🌟 𝐍𝐞𝐰 𝐚𝐫𝐭𝐢𝐜𝐥𝐞: 𝐭𝐡𝐞 𝐜𝐨𝐧𝐧𝐞𝐜𝐭𝐢𝐨𝐧 𝐛𝐞𝐭𝐰𝐞𝐞𝐧 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, 𝐌𝐲𝐚𝐥𝐠𝐢𝐜 𝐄𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬 𝐚𝐧𝐝 𝐩𝐨𝐬𝐭-𝐯𝐚𝐜𝐜𝐢𝐧𝐚𝐥 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞𝐬 𝐥𝐢𝐞𝐬 𝐢𝐧 𝐭𝐡𝐞 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐨𝐟 𝐚𝐧 𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐇𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐜 𝐒𝐲𝐧𝐝𝐫𝐨𝐦𝐞🌟

🌐 I am excited to share with you our latest paper entitled "𝐇𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐜 𝐀𝐒𝐈𝐀: 𝐀 𝐯𝐚𝐜𝐜𝐢𝐧𝐞- 𝐚𝐧𝐝 𝐜𝐡𝐫𝐨𝐧𝐢𝐜 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧-𝐢𝐧𝐝𝐮𝐜𝐞𝐝 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞 𝐛𝐞𝐡𝐢𝐧𝐝 𝐭𝐡𝐞 𝐨𝐫𝐢𝐠𝐢𝐧 𝐨𝐟 𝐥𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐦𝐲𝐚𝐥𝐠𝐢𝐜 𝐞𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬". In this paper, we explain the links between Long COVID, Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (ME/CFS) and COVID-19 post-vaccine syndromes. 🤔 Stay reading to the end and you will also find our treatment proposal that could improve symptoms.💊

➡️𝐋𝐢𝐧𝐤 𝐨𝐟 𝐨𝐮𝐫 𝐫𝐞𝐯𝐢𝐞𝐰 𝐚𝐫𝐭𝐢𝐜𝐥𝐞:

🔍 𝐀𝐛𝐬𝐭𝐫𝐚𝐜𝐭: We present a model for the development of these diseases that involves a complex interplay between immune hyperactivation, autoimmune hypophysitis or pituitary hypofunction, and immune exhaustion. We believe that the starting point is a deficient CD4 T-cell response to viral infections in genetically predisposed individuals (HLA-DRB1). This would follow from an uncontrolled immune response with hyperactivation of CD8 T cells and elevated antibody production, some of which could be directed against self-antigens, triggering autoimmune hypophysitis or direct damage to the pituitary, resulting in decreased production of pituitary hormones, such as ACTH. 🧬

🔬 𝐖𝐡𝐚𝐭'𝐬 𝐭𝐡𝐞 𝐛𝐢𝐠 𝐝𝐞𝐚𝐥?
1️⃣ 𝐑𝐞𝐥𝐚𝐭𝐢𝐨𝐧𝐬𝐡𝐢𝐩 𝐭𝐨 𝐀𝐒𝐈𝐀 𝐒𝐲𝐧𝐝𝐫𝐨𝐦𝐞: We propose that Long COVID, ME/CFS and post-vaccine COVID-19 syndrome could be included in adjuvant-induced autoimmune/inflammatory syndrome (ASIA) due to their similar clinical manifestations and possible relationship to genetic factors, such as polymorphisms in the HLA-DRB1 gene.
2️⃣ 𝐃𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭𝐚𝐥 𝐌𝐨𝐝𝐞𝐥: We suggest that these diseases begin with a deficient immune response and progress to uncontrolled immune hyperactivation, followed by immune exhaustion, exacerbating symptoms and pathology.
3️⃣ 𝐇𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐚: We highlight the decrease in ACTH production and its impact on immune function and clinical symptoms, establishing a direct link with pituitary dysfunction.
4️⃣ 𝐓𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭 𝐏𝐫𝐨𝐩𝐨𝐬𝐚𝐥: We propose a treatment approach including antivirals, corticosteroids/ginseng, antioxidants and metabolic precursors to improve symptoms by modulating immune response, pituitary function, inflammation and oxidative stress.

💡 𝐈𝐦𝐩𝐥𝐢𝐜𝐚𝐭𝐢𝐨𝐧𝐬 𝐚𝐧𝐝 𝐂𝐨𝐧𝐜𝐥𝐮𝐬𝐢𝐨𝐧𝐬:
🔹These disorders could have an autoimmune origin against the adenohypophysis.
🔹Treatment with antivirals and corticosteroid replacement therapy in patients with permanent pituitary damage could improve symptoms by addressing immune and hormonal dysfunction.

🧠 𝐓𝐡𝐞 𝐤𝐞𝐲 𝐢𝐬 𝐩𝐢𝐭𝐮𝐢𝐭𝐚𝐫𝐲 𝐝𝐚𝐦𝐚𝐠𝐞: 𝐡𝐨𝐰 𝐝𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐫𝐞𝐥𝐚𝐭𝐞 𝐭𝐨 𝐭𝐡𝐞 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐨𝐟 𝐌𝐄/𝐂𝐅𝐒, 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐨𝐭𝐡𝐞𝐫 𝐩𝐨𝐬𝐭-𝐯𝐢𝐫𝐚𝐥 𝐚𝐧𝐝 𝐩𝐨𝐬𝐭-𝐯𝐚𝐜𝐜𝐢𝐧𝐞 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞𝐬?

💉 Certain viruses (and other pathogens) and vaccines can affect the pituitary gland, interfering with cortisol production and triggering a cascade of complex symptoms. In patients with weak HLA-DRB1 alleles, such as DR15, immune hyperactivation can trigger an autoimmune response against ACTH, crucial for cortisol production. This is exactly analogous to how other autoimmune diseases such as multiple sclerosis or lupus develop, where the immune system attacks other antigens in the body, but in the syndromes we are discussing, the autoimmunity is specifically directed against pituitary ACTH.

🦠 This link explains why patients with chronic infections often experience persistent hypocortisolemia, as the pathogen continues to produce ACTH-mimicking antigens, maintaining the active autoimmune response or generates direct pituitary damage. In contrast, patients without chronic infections and with the same weak alleles treated with immune checkpoint inhibitors (ICIs) may develop temporary hypophysitis and similar cortisol deficits, but discontinuation of treatment usually allows recovery.

This also explains why patients experience chronic fatigue, dysautonomia, orthostatic intolerance, exercise intolerance, intolerance to stressful events and mild hypoglycemia due to low cortisol. Cortisol is crucial in providing the body with needed energy and regulating the stress response. When cortisol levels are low, as they are in these syndromes, the body cannot respond effectively to physical and emotional demands.

🩸Cortisol plays a crucial role in maintaining stable blood sugar levels by promoting gluconeogenesis (glucose production) and stimulating the release of stored glucose in the form of glycogen in the liver. When there is insufficient cortisol, the body faces difficulties in increasing glucose levels in demand situations, such as during physical exercise or in response to stress, which can lead to episodes of mild hypoglycemia. In times of fright or anger, adrenaline release may temporarily improve symptoms by temporarily increasing glucose availability, briefly compensating for cortisol deficiency. However, this response does not adequately replace the long-term regulatory functions of cortisol, so symptoms may return once adrenaline subsides.

🏋️‍♂️ In the case of physical exercise, which naturally increases cortisol levels to mobilize energy and respond to physical exertion, the lack of this hormone limits the body's ability to maintain sustained physical activity. Patients may experience rapid muscle fatigue, feelings of weakness and slower recovery after exercise.

😰 As for stressful events (exams, travel, surgical operations, etc) , cortisol also plays a crucial role in the body's response to emotional or physical stress. When cortisol levels are insufficient, the body has difficulty handling stressful situations effectively. This can manifest itself in an exacerbation of existing symptoms, such as intense fatigue, dizziness, difficulty concentrating and a generalized feeling of malaise.

➡️ For years, many of these patients have been misunderstood and mislabeled as having psychosomatic illness. This is because their symptoms tend to worsen during periods of stress, which has led to the suggestion that the origin of their problems lies in psychological factors. However, the reality is that these patients are not experiencing symptoms due to an underlying psychological disorder, but as a direct result of insufficient cortisol. The lack of this vital hormone prevents the body from adapting and responding appropriately to stress, which perpetuates and aggravates their physical symptoms.

🚨 𝐓𝐡𝐞 𝐃𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐨𝐟 𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐢𝐭𝐲 𝐭𝐨 𝐀𝐂𝐓𝐇: 𝐀 𝐏𝐫𝐨𝐜𝐞𝐬𝐬 𝐒𝐢𝐦𝐢𝐥𝐚𝐫 𝐭𝐨 𝐎𝐭𝐡𝐞𝐫 𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐃𝐢𝐬𝐞𝐚𝐬𝐞𝐬 𝐬𝐮𝐜𝐡 𝐚𝐬 𝐌𝐮𝐥𝐭𝐢𝐩𝐥𝐞 𝐒𝐜𝐥𝐞𝐫𝐨𝐬𝐢𝐬 🚨

This same mechanism occurs in other autoimmune diseases. Some HLA-II alleles, such as the DR15 variant, are associated with an impaired ability to recognize cells infected with certain pathogens, such as Epstein-Barr virus (EBV). In multiple sclerosis this poor recognition ability specifically affects CD4 T cells, which are crucial for coordinating the immune response. When CD4 T cells cannot correctly recognize infected cells, this leads to hyperactivation of CD8 T cells and an increase in antibodies against the pathogen to compensate for the deficient CD4 T cell response. Without the coordinated help of CD4 T cells, CD8 T cells cannot eliminate all EBV-infected cells, thus never effectively eliminating or controlling the infection and resulting in chronic infection. This results in an increase of infected cells, an exhaustion of CD8 T cells and an increased risk of developing autoimmune diseases, since CD4 T cells, by misrecognizing these viral antigens presented on the HLA-II antigen-presenting cells, can confuse them with the body's own proteins, generating an autoimmune disease. In multiple sclerosis, autoimmunity develops when the EBNA-1 antigen of the Epstein-Barr virus is mistaken for myelin, due to a similar amino acid sequence and molecular mimicry in patients with DR15 alleles. The same could occur in patients with Long COVID, myalgic encephalomyelitis and post-vaccinal syndromes, where autoimmunity against ACTH develops.

#LongCovid #MECFS #Vaccinesfrontiersin.org/journals/immun… 📢 𝐖𝐡𝐲 𝐕𝐚𝐜𝐜𝐢𝐧𝐞𝐬 𝐂𝐚𝐧 𝐃𝐞𝐯𝐞𝐥𝐨𝐩 𝐏𝐚𝐭𝐡𝐨𝐥𝐨𝐠𝐢𝐞𝐬 𝐒𝐢𝐦𝐢𝐥𝐚𝐫 𝐭𝐨 𝐏𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐏𝐨𝐬𝐭-𝐈𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐮𝐬 𝐌𝐄/𝐂𝐅𝐒? 📢

🔬 𝐂𝐨𝐦𝐦𝐨𝐧 𝐌𝐞𝐜𝐡𝐚𝐧𝐢𝐬𝐦: 𝐔𝐧𝐜𝐨𝐧𝐭𝐫𝐨𝐥𝐥𝐞𝐝 𝐈𝐦𝐦𝐮𝐧𝐞 𝐀𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧.
Both persistent COVID and post-infectious ME/CFS and post-vaccine syndrome share a common basis: an overactive immune response. In our study, we propose the presence of:

1️⃣ 𝐏𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐜𝐞 𝐨𝐟 𝐕𝐢𝐫𝐚𝐥 𝐀𝐧𝐭𝐢𝐠𝐞𝐧𝐬 𝐨𝐫 𝐀𝐝𝐣𝐮𝐯𝐚𝐧𝐭𝐬:
▪️ 𝐂𝐡𝐫𝐨𝐧𝐢𝐜 𝐯𝐢𝐫𝐚𝐥 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧: after a viral infection, such as SARS-CoV-2 or Epstein-Barr virus (EBV), viral antigens may remain in the body, triggering a continuous immune response.
▪️ 𝐕𝐚𝐜𝐜𝐢𝐧𝐚𝐭𝐢𝐨𝐧: Vaccines contain adjuvants designed to stimulate the immune system. In genetically predisposed individuals (HLA-DRB1), this stimulation may be excessive, leading to uncontrolled immune activation similar to a viral infection. In addition, the introduced viral antigens could have molecular mimicry with ACTH, exacerbating the immune response and potentially contributing to the development of autoimmunity against ACTH.

2️⃣ 𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐢𝐭𝐲 𝐀𝐠𝐚𝐢𝐧𝐬𝐭 𝐭𝐡𝐞 𝐀𝐝𝐞𝐧𝐨𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐬:
* Both conditions can lead to autoimmune inflammation of the adenohypophysis (autoimmune hypophysitis), resulting in hormonal dysfunction, especially ACTH production.

3️⃣ 𝐇𝐲𝐩𝐞𝐫𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐞𝐦𝐢𝐚 𝐚𝐧𝐝 𝐇𝐏𝐀 𝐀𝐱𝐢𝐬 𝐇𝐲𝐩𝐨𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧:
* Chronic inflammation and proinflammatory cytokine production can alter the hypothalamic-pituitary-adrenal (HPA) axis, leading to low cortisol levels, which exacerbate fatigue and other symptoms.

🔄 𝐂𝐲𝐜𝐥𝐞 𝐨𝐟 𝐇𝐲𝐩𝐞𝐫𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 𝐚𝐧𝐝 𝐈𝐦𝐦𝐮𝐧𝐞 𝐃𝐞𝐩𝐥𝐞𝐭𝐢𝐨𝐧:
▪️ 𝐈𝐧𝐢𝐭𝐢𝐚𝐥 𝐇𝐲𝐩𝐞𝐫𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧: Initial immune response is excessive, with high cytokine production and CD8 T-cell activation.
▪️ 𝐈𝐦𝐦𝐮𝐧𝐞 𝐞𝐱𝐡𝐚𝐮𝐬𝐭𝐢𝐨𝐧: Over time, this hyperactivation leads to T-cell exhaustion, decreasing the body's ability to control infection and exacerbating the pathology.
▪️ 𝐇𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦: Insufficient cortisol maintains the state of immune hyperactivation, perpetuating inflammation and hindering resolution of the immune cycle.

📊 𝐄𝐯𝐢𝐝𝐞𝐧𝐜𝐞 𝐚𝐧𝐝 𝐂𝐥𝐢𝐧𝐢𝐜𝐚𝐥 𝐒𝐢𝐦𝐢𝐥𝐚𝐫𝐢𝐭𝐢𝐞𝐬:
▪️ 𝐒𝐡𝐚𝐫𝐞𝐝 𝐒𝐲𝐦𝐩𝐭𝐨𝐦𝐬: chronic fatigue, muscle and joint pain, sleep disturbances, cognitive problems, and post-exertional malaise.
▪️ 𝐂𝐨𝐦𝐦𝐨𝐧 𝐆𝐞𝐧𝐞𝐭𝐢𝐜: Polymorphisms in the HLA-DRB1 gene predispose to an exaggerated immune response to both viral infections and vaccine components.

🔍 𝐂𝐨𝐧𝐜𝐥𝐮𝐬𝐢𝐨𝐧: Our review suggests that both Long COVID and post-infectious ME/CFS and post-vaccination syndromes could be considered as part of the autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA). These findings underline the need for a personalized therapeutic approach that takes into account the genetic predisposition and immune status of the patient.

🌍💉 𝐇𝐨𝐰 𝐂𝐚𝐧 𝐒𝐨𝐦𝐞 𝐕𝐚𝐜𝐜𝐢𝐧𝐞𝐬 𝐓𝐫𝐢𝐠𝐠𝐞𝐫 𝐏𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐇𝐞𝐚𝐥𝐭𝐡 𝐏𝐫𝐨𝐛𝐥𝐞𝐦𝐬? 💉🌍
1️⃣ 𝐌𝐞𝐜𝐡𝐚𝐧𝐢𝐬𝐦 𝐨𝐟 𝐀𝐜𝐭𝐢𝐨𝐧:
▪️ Vaccines contain adjuvants and antigens designed to stimulate robust immune responses.
▪️ In some cases, this stimulation can lead to a dysregulated autoimmune response, similar to that seen in diseases such as systemic lupus erythematosus.

2️⃣ 𝐕𝐚𝐜𝐜𝐢𝐧𝐞𝐬 𝐈𝐧𝐯𝐨𝐥𝐯𝐞𝐝:
▪️ COVID-19: Cases of prolonged symptoms after infection or vaccination, known as Long COVID or post-COVID syndrome, have been reported.
▪️ Hepatitis B and C, HPV: Some individuals develop ME/CFS after vaccination, related to autoimmunity and immune alterations.

3️⃣ 𝐑𝐢𝐬𝐤 𝐅𝐚𝐜𝐭𝐨𝐫𝐬:
▪️ Genetic predisposition such as polymorphisms in the HLA-DRB1 gene may increase susceptibility to abnormal immune responses.
▪️ Viral persistence or chronic antigen exposure may trigger a continuous and pathologic immune response.

🌍💉 𝐃𝐢𝐝 𝐲𝐨𝐮 𝐤𝐧𝐨𝐰 𝐭𝐡𝐚𝐭 𝐯𝐚𝐜𝐜𝐢𝐧𝐞𝐬 𝐝𝐞𝐬𝐢𝐠𝐧𝐞𝐝 𝐰𝐢𝐭𝐡 𝐚𝐝𝐞𝐧𝐨𝐯𝐢𝐫𝐮𝐬𝐞𝐬 𝐦𝐚𝐲 𝐡𝐚𝐯𝐞 𝐚 𝐬𝐥𝐢𝐠𝐡𝐭𝐥𝐲 𝐢𝐧𝐜𝐫𝐞𝐚𝐬𝐞𝐝 𝐫𝐢𝐬𝐤 𝐨𝐟 𝐭𝐫𝐢𝐠𝐠𝐞𝐫𝐢𝐧𝐠 𝐩𝐫𝐨𝐥𝐨𝐧𝐠𝐞𝐝 𝐢𝐦𝐦𝐮𝐧𝐞 𝐫𝐞𝐬𝐩𝐨𝐧𝐬𝐞𝐬 𝐜𝐨𝐦𝐩𝐚𝐫𝐞𝐝 𝐭𝐨 𝐦𝐞𝐬𝐬𝐞𝐧𝐠𝐞𝐫 𝐑𝐍𝐀 𝐯𝐚𝐜𝐜𝐢𝐧𝐞𝐬?

Adenoviruses used as vectors may persist longer in the body, exposing the immune system to viral components for extended periods.

🦠Adenoviruses are linear double-stranded DNA viruses and remain in an episomal condition in the nucleus. The mechanism of adenovirus vector persistence has not yet been elucidated. But they can persist for a long time in the organism. It is thought that it could be by their integration into the genome or by episomal gene duplication facilitated by the transcription machinery of the host cells. That is, it could happen that it transmits episomes to its cells as occurs in Epstein-Barr virus without lytic phase. During mitosis, EBV episomes are bound to chromosomes in metaphase through EBNA-1, allowing efficient segregation of episomes into daughter cells.

🔬 This theoretical phenomenon could predispose certain genetically susceptible individuals to develop chronic autoimmune or inflammatory disorders, as discussed in the context of ASIA syndrome. In contrast, messenger RNA vaccines, by rapidly degrading after inducing the desired immune response, limit this prolonged exposure.

💉⚠️ Regardless of the type of vaccine against COVID-19 or other pathologies, whether messenger RNA or adenoviral vector, there is a theoretical possible risk of developing autoimmune disease only in individuals with certain genetic alleles, such as HLA-DRB1. The key lies in prolonged exposure to viral antigens, which could trigger persistent autoimmune responses.

🔬 mRNA vaccines are characterized by rapidly degrading after inducing the desired immune response, thus limiting prolonged exposure to viral components. In contrast, adenoviral vector-based vaccines can persist in the body longer, potentially increasing the risk of a longer-lasting autoimmune reaction in susceptible individuals.

💡 It is crucial to remember that these risks are rare when compared to the total number of vaccinated individuals and that all vaccines, including adenovirus and messenger RNA vaccines, are critical to combat pandemic diseases such as COVID-19 at the species level. However, understanding these differences may help improve future vaccine design and surveillance for potential adverse effects in these susceptible individuals.

🌟 Recall that vaccines save millions of lives and prevent serious consequences of infections in the majority of the population. However, it is crucial to recognize that they may also present risks in some susceptible individuals.

🧬💉 HLA-DRB1 genetic alleles play a crucial role in predisposition to diseases such as Long COVID, myalgic encephalomyelitis (ME/CFS) and ASIA syndrome, as well as in post-vaccine syndromes.

🔍 These HLA-DRB1 alleles are part of the HLA (human leukocyte antigen) system, which regulates how the immune system recognizes and responds to foreign antigens, such as viruses and vaccine components. In individuals with certain HLA-DRB1 alleles, the immune system may trigger excessive or inappropriate responses to these antigens, leading to autoimmune conditions and inflammatory syndromes.

🦠 This explains why some patients, after significant viral infection or vaccination, may develop persistent autoimmune reactions. In the case of Long COVID and ME/CFS, persistence of viral antigens could trigger an autoimmune response against self tissues, including the pituitary gland.

🔍✨ In a 𝐤𝐞𝐲 𝐬𝐭𝐮𝐝𝐲, patients who developed hypophysitis after infection with the first SARS-CoV recovered their health months after treatment with replacement corticosteroids. This finding underscores the importance of detecting hypophysitis early to prevent permanent damage.➡️

🧠 Hypophysitis can cause a decrease in ACTH production, crucial for adrenal function and immune response. Controlling ACTH levels is critical if symptoms such as chronic fatigue, orthostatic hypotension and sleep disturbances are present after a viral infection.

💊 Early administration of replacement corticosteroids can stop ACTH secretion and prevent autoimmunity against this hormone, thus protecting the pituitary from further damage. Over time, as hypophysitis and viral infection subside, the dose of replacement corticosteroids can be gradually reduced until normal pituitary function is restored.

🔍Challenges in HPA Axis Evaluation in Patients with Long COVID, ME/CFS and Post-Vaccine Syndromes.
Studies are often limited to single morning cortisol measurements, ignoring diurnal variability and cortisol response to physical/mental stress, which may underestimate problems in the HPA axis. In addition, CRH or ACTH stimulation tests, crucial for assessing pituitary and adrenal function, are not frequently performed.

It is crucial to detect HPA axis dysfunctions as early as possible to prevent adrenal atrophy due to low ACTH levels. Newly diagnosed patients may recover HPA axis function if autoimmune or direct damage by infection to the pituitary is detected early. Conversely, as time passes, the risk of pituitary damage from autoimmunity against ACTH increases, leading to further adrenal atrophy and the need for hydrocortisone replacement therapy. Early detection and treatment of these dysfunctions is crucial to improve the clinical management and quality of life of these patients.

#Research #Health #Autoimmunityncbi.nlm.nih.gov/pmc/articles/P…

🔴Nuevo artículo confirma lo que hemos discutido: ¡𝐥𝐨𝐬 𝐭𝐞𝐬𝐭 𝐝𝐞 𝐦𝐢𝐜𝐫𝐨𝐛𝐢𝐨𝐭𝐚 𝐬𝐨𝐧 𝐢𝐧𝐮́𝐭𝐢𝐥𝐞𝐬! El mundo de la microbiota está siendo explotado como una estafa, especialmente entre pacientes desesperados por resolver problemas intestinales. Aquí te explico: 1/La diversidad de microbiota varía entre personas, lo que hace imposible obtener resultados consistentes de los test de microbiota. No se sabe cuál es la microbiota normal. #Microbiota #SIBO #LongEBV #microE2324

🦠 🔍 𝐃𝐢𝐝 𝐲𝐨𝐮 𝐤𝐧𝐨𝐰 𝐭𝐡𝐚𝐭 𝐄𝐬𝐩𝐭𝐞𝐢𝐧-𝐁𝐚𝐫𝐫 𝐯𝐢𝐫𝐮𝐬 𝐜𝐨𝐮𝐥𝐝 𝐛𝐞 𝐚 𝐭𝐫𝐢𝐠𝐠𝐞𝐫 𝐟𝐨𝐫 𝐬𝐲𝐦𝐩𝐭𝐨𝐦𝐬 𝐢𝐧 𝐌𝐄/𝐂𝐅𝐒 𝐚𝐧𝐝 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃?
A thread 🧵

Below, I summarize the points of our recent published review and how it could explain the development of 𝐝𝐲𝐬𝐚𝐮𝐭𝐨𝐧𝐨𝐦𝐢𝐚, 𝐦𝐢𝐜𝐫𝐨𝐜𝐥𝐨𝐭𝐬, 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐝𝐢𝐬𝐞𝐚𝐬𝐞𝐬, 𝐞𝐱𝐞𝐫𝐜𝐢𝐬𝐞 𝐢𝐧𝐭𝐨𝐥𝐞𝐫𝐚𝐧𝐜𝐞, 𝐦𝐢𝐭𝐨𝐜𝐡𝐨𝐧𝐝𝐫𝐢𝐚𝐥 𝐝𝐲𝐬𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧, 𝐡𝐲𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦 𝐚𝐧𝐝 𝐦𝐨𝐫𝐞 𝐜𝐨𝐧𝐬𝐞𝐪𝐮𝐞𝐧𝐜𝐞𝐬. Share with other patients so they can understand their illness. 𝐊𝐧𝐨𝐰𝐥𝐞𝐝𝐠𝐞 𝐢𝐬 𝐩𝐨𝐰𝐞𝐫! 📚

Many people wonder why EBV, the Epstein-Barr virus, and not another virus, is the main trigger of the symptomatic picture of ME/CFS and Long COVID, when there are other factors, such as different infections, metal intoxication, among others. In the following lines, I will explain the fundamentals of this phenomenon, summarizing the essential points of the review article we recently published.

The common denominator of all the triggering factors of both diseases is their capacity to immunosuppress. Any intracellular infection, whether bacterial, viral or parasitic, that is not controlled, leads to immunosuppression due to chronic exposure to antigens. Usually, the ability to control an infection is due to genetic factors, particularly the HLA genes (I and II). These genes encode proteins called human leukocyte antigen (HLA), which are essential for distinguishing self from non-self in our body. If this "alert" does not function properly, the immune system cannot efficiently eliminate pathogens. HLAs are like a scanner that allows us to identify things that are not from the body and respond to them. If this scanner is not working properly and does not recognize something that is bad, it would prevent your immune system from eliminating it and therefore prevent it from moving freely through your body without being eliminated.
In the context of ME/CFS, there are 𝐭𝐰𝐨 𝐩𝐨𝐬𝐬𝐢𝐛𝐥𝐞 𝐬𝐜𝐞𝐧𝐚𝐫𝐢𝐨𝐬: the individual may have a direct genetic predisposition to EBV, or they may lose control over EBV due to an underlying immune deficiency caused by another infection or exposure to chemicals or metals. If it is another infection, we would also be talking about a "genetic weakness" (HLA) to those specific pathogens.
If the individual is genetically susceptible to EBV, it is because he or she has old HLA-II haplotypes, to which EBV has co-evolved. This is mainly because EBV infects by binding to HLA-II proteins in cells. This virus is cunning: when it infects a cell, it introduces its DNA into it latently without generating new virions, avoiding detection by the immune system and using B cells as "Trojan horses".

While 95% of the world's population has EBV, only a minority develop problems. This is where the "weak" HLA-II haplotypes against EBV come into play again.
Although it is said that the majority of the population does not have problems with this virus, this is not entirely true. Think that this virus takes advantage of every time you become immunosuppressed for any reason. An example is its brother herpes labialis, that every time that person is immunosuppressed for any reason, it takes advantage and infects more cells, making the lesion visible on the lips. But every time the immune system recovers from the first event that immunosuppressed him, this virus is controlled again and the lesion disappears. This is exactly the same thing that happens in healthy people who are able to control EBV.

The main difference between these healthy people and ME/CFS patients who have problems with EBV, is that by having strong HLA-II haplotypes against EBV they are able to recognize all EBV latency types and control them. In contrast, 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐰𝐢𝐭𝐡 𝐄𝐁𝐕 𝐌𝐄/𝐂𝐅𝐒, 𝐡𝐚𝐯𝐢𝐧𝐠 𝐰𝐞𝐚𝐤 𝐡𝐚𝐩𝐥𝐨𝐭𝐲𝐩𝐞𝐬 𝐚𝐠𝐚𝐢𝐧𝐬𝐭 𝐄𝐁𝐕, 𝐭𝐡𝐞𝐢𝐫 𝐓𝐂𝐃𝟒 𝐜𝐞𝐥𝐥𝐬 𝐚𝐫𝐞 𝐧𝐨𝐭 𝐚𝐛𝐥𝐞 𝐭𝐨 𝐫𝐞𝐜𝐨𝐠𝐧𝐢𝐳𝐞 𝐄𝐁𝐕 𝐥𝐚𝐭𝐞𝐧𝐜𝐲 𝐈 𝐜𝐞𝐥𝐥𝐬. The rest of the latency types are able to be recognized since they are controlled by TCD8 cells, as they would not have weak HLA-I haplotypes against EBV.

Let us explain this better. TCD4 cells recognize antigens presented on HLA-II proteins and TCD8 cells recognize antigens presented on HLA-I proteins. Normally, any intracellular infection is controlled by TCD8 cells because the infected cells present on the HLA-I proteins of their membrane the antigens of the pathogen inside. On the other hand, HLA-II proteins are found mostly on antigen-presenting cells that take antigens from outside the cell and present them on their HLA-II proteins so that they are recognized by T-CD4 cells. So, we would think that EBV, being an intracellular pathogen, its antigens should always be presented on the HLA-I proteins of the infected cell. This is not always the case; this virus has evolved to evade this system by generating latency. One of the evasion mechanisms to remain unrecognized is to prevent a latency antigen, called EBNA-1, from being presented on HLA-I proteins and from being presented on HLA-II proteins. This is of utmost importance for the virus because it prevents, for example, latency I cells (only expressing EBNA-1 from the virus) from being recognized by TCD8 cells. On the other hand, the rest of the latency cells (II and III) and lytic cells without would be recognized and eliminated by CD8 T cells. So we would think that no one would be able to control the latency I cells if they evade CD8 T cells. Here our immune system is also intelligent and this is where CD4 T cells play the differential role between healthy and sick people with this virus. The importance of HLA-II haplotypes reappears. Those individuals with EBV-resistant HLA-II haplotypes will be able to present the EBNA-1 antigen well on latency I cells and will be recognized and eliminated by TCD4 cells. In contrast, those with EBV-weak HLA-II haplotypes will not be able to present EBNA-1 well on HLA-II proteins and therefore CD4 T cells will not recognize the latency I cells. These latency I cells, when left unchecked, will multiply and cause inflammation and damage. But every time they go to another type of latency or lytic phase they will be recognized by CD8 T cells.

𝐒𝐨 𝐰𝐡𝐚𝐭 𝐡𝐚𝐩𝐩𝐞𝐧𝐬 𝐭𝐨 𝐭𝐡𝐨𝐬𝐞 𝐢𝐧𝐝𝐢𝐯𝐢𝐝𝐮𝐚𝐥𝐬 𝐰𝐡𝐨 𝐡𝐚𝐯𝐞 𝐛𝐞𝐞𝐧 𝐢𝐧𝐟𝐞𝐜𝐭𝐞𝐝 𝐰𝐢𝐭𝐡 𝐨𝐭𝐡𝐞𝐫 𝐩𝐚𝐭𝐡𝐨𝐠𝐞𝐧𝐬 (𝐬𝐮𝐜𝐡 𝐚𝐬 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃) 𝐚𝐧𝐝 𝐟𝐚𝐢𝐥 𝐭𝐨 𝐜𝐨𝐧𝐭𝐫𝐨𝐥 𝐭𝐡𝐞𝐦? Well, in the end the same thing happens. Being genetically weak against these pathogens, they also end up presenting an immunodeficiency due to chronic exposure to antigens, decreasing the effective response of CD4 T cells. As these cells are the main cells that control EBV latency I, cells with latency I end up evading the immune system and multiplying, generating the same problems as in the case of EBV ME/CFS.

Therefore, in any subtype of patient with ME/CFS and in Long COVID, they end up presenting a viral syndrome due to EBV. Once EBV latency I cells are out of control, it allows any inflammatory stimulus in any tissue to recruit leukocytes (including EBV latency cells), ultimately leading to the 𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐄𝐁𝐕-𝐢𝐧𝐟𝐞𝐜𝐭𝐞𝐝 𝐞𝐜𝐭𝐨𝐩𝐢𝐜 𝐥𝐲𝐦𝐩𝐡𝐨𝐢𝐝 𝐚𝐠𝐠𝐫𝐞𝐠𝐚𝐭𝐞𝐬.

These formations are "ectopic" because they are outside their usual location, i.e., they do not form in primary (such as thymus and bone marrow) or secondary (such as lymph nodes and spleen) lymphoid tissues. They form transiently to cope with infection or inflammation and disappear when the stimulus is resolved.

The B cells with EBV latency use these lymphoid aggregates to their advantage, since as there is antigen presentation in these structures, they take advantage of it to pass from latency to lytic phase, generating foci of viral reactivations in these inflamed tissues. This causes that, although the initial inflammatory stimulus that provoked the formation of these aggregates has been resolved, these aggregates remain continuously in these tissues due to another inflammatory stimulus due to the molecules released by the cells with latency, as well as the viral reactivations. This would occur mainly in the mucous membranes of our organism but can occur in different tissues and would be the basis for the 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐨𝐟 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐝𝐢𝐬𝐞𝐚𝐬𝐞𝐬.

These autoimmune diseases are generated due to the presentation of cellular autoantigens from those tissues or by the presentation of viral EBNA-1 through HLA-II proteins. The antigens when presented on HLA-II proteins undergo a series of modifications that can lead to the formation of new antigens "different" from the previous ones. In addition, EBNA-1 has a sequence similar to different proteins in our body, which can confuse our immune system and generate an autoimmune response. Here again appears the implication of having weak HLA-II haplotypes against EBV, since most of the diseases associated with this virus such as multiple sclerosis, lupus, rheumatoid arthritis, Sjögren's, etc. are associated with the same old HLA-II haplotypes as those weak against EBV. So having these autoimmune diseases implies that they do not control well these cells with EBV latency and therefore are responsible for the development of their autoimmunity.

𝐖𝐡𝐲 𝐝𝐨 𝐰𝐨𝐦𝐞𝐧 𝐡𝐚𝐯𝐞 𝐚 𝐡𝐢𝐠𝐡𝐞𝐫 𝐩𝐫𝐞𝐯𝐚𝐥𝐞𝐧𝐜𝐞 𝐨𝐟 𝐌𝐄/𝐂𝐅𝐒, 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐝𝐢𝐬𝐞𝐚𝐬𝐞𝐬?
Hormones play a crucial role. Estrogens, in particular, affect the CD4/CD8 T-cell ratio by reducing it, increase B-cell longevity, enhance antibody release and amplify the expression of HLA-II proteins. Under normal conditions, this increase in antibody levels in women enhances their resistance to viral infections. However, under pathological circumstances, this hormonal balance leads to a prolonged survival of B cells and a decrease in CD4 T cells, in addition to intensifying the expression of HLA-II. This situation leads to increased vulnerability to EBV due to increased survival of virus-transformed B cells and increased expression of HLA-II, which facilitates infection of a greater number of cells. In addition, elevated HLA-II expression can lead to a more robust presentation of cellular autoantigens or viral antigens that, after undergoing post-translational changes, generate neoantigens. These can activate autoreactive cells. Therefore, both the increased survival of transformed B cells and the increased antigenic presentation generated by the increased expression of HLA-II by estradiol may favor an increase in the presentation of both self and foreign antigens during an infectious process, and those abnormal plasma cells that produce autoantibodies survive longer, which consequently increases the likelihood of women developing autoimmune diseases or even cancer.

On the male side, testosterone modulates the immune system by promoting CD4 Th1 (antiviral) response and CD8 T-cell activation, while inhibiting NK cell response and HLA-II expression. Since antigen-presenting cells are essential for the differentiation of CD4 T cells toward Th1 or Th2, based on the cytokines they release, sex hormones may influence this differentiation. Women, having higher levels of antibodies (Th2 response), show a more efficient response to extracellular infections. However, against intracellular pathogens, their immune system may not be as efficient as the male immune system, which benefits from a stronger Th1 cellular response to fight virus-infected cells.

𝐃𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐦𝐨𝐝𝐞𝐥 𝐞𝐱𝐩𝐥𝐚𝐢𝐧 𝐭𝐡𝐞 𝐨𝐯𝐞𝐫𝐚𝐜𝐭𝐢𝐯𝐞 𝐲𝐞𝐭 𝐢𝐧𝐞𝐟𝐟𝐞𝐜𝐭𝐢𝐯𝐞 𝐢𝐦𝐦𝐮𝐧𝐞 𝐫𝐞𝐬𝐩𝐨𝐧𝐬𝐞?
Yes, this model describes a situation in which the body's immune system is working excessively, but inefficiently, against the EBV virus:

1️⃣ 𝐃𝐞𝐟𝐢𝐜𝐢𝐞𝐧𝐭 𝐚𝐝𝐚𝐩𝐭𝐢𝐯𝐞 𝐫𝐞𝐬𝐩𝐨𝐧𝐬𝐞: CD4 T cells, are not correctly recognizing and dealing with EBV latency I cells. This leads to more infected cells circulating and, at the same time, to a fatigue or exhaustion of the T cells, reducing their ability to fight the virus.

2️⃣ 𝐎𝐯𝐞𝐫-𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐢𝐧𝐧𝐚𝐭𝐞 𝐢𝐦𝐦𝐮𝐧𝐢𝐭𝐲: Because of this failure of the adaptive response, another part of the immune system, called innate immunity, becomes over-activated because it continually detects that there is an infection but that it cannot be resolved by adaptive immunity. This results in the constant production of inflammatory substances that, instead of helping, can generate more problems and maintain chronic inflammation.

3️⃣ 𝐈𝐦𝐛𝐚𝐥𝐚𝐧𝐜𝐞 𝐢𝐧 𝐢𝐦𝐦𝐮𝐧𝐞 𝐫𝐞𝐬𝐩𝐨𝐧𝐬𝐞𝐬: The body tends to favor an immune response (known as Th2) that is not best suited to fight this type of infection. This is due in part to the production of a substance called IL-6, which redirects the body's defensive response towards the production of antibodies instead of an antiviral cellular response (Th1). The increased Th2 response favors the latency and lytic cycles of EBV by activating more B cells.

𝐃𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐦𝐨𝐝𝐞𝐥 𝐞𝐱𝐩𝐥𝐚𝐢𝐧 𝐯𝐢𝐫𝐚𝐥 𝐫𝐞𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧𝐬 𝐚𝐧𝐝 𝐭𝐡𝐚𝐭 𝐨𝐟 𝐨𝐭𝐡𝐞𝐫 𝐥𝐚𝐭𝐞𝐧𝐭 𝐩𝐚𝐭𝐡𝐨𝐠𝐞𝐧𝐬?
Yes, the model explains that, due to decreased activation and function of cytotoxic CD4 T cells, there is a loss of immune surveillance over latent infections of other pathogens. These CD4 T cells are necessary to control latent or lytic phase cells of pathogens such as Parvovirus B19, EBV, cytomegalovirus and other herpesviruses. As a result, increased viral reactivation will be observed, especially in individuals with a higher degree of immunodeficiency.

𝐃𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐦𝐨𝐝𝐞𝐥 𝐞𝐱𝐩𝐥𝐚𝐢𝐧 𝐡𝐨𝐰 𝐭𝐡𝐞𝐫𝐞 𝐜𝐨𝐮𝐥𝐝 𝐛𝐞 𝐢𝐧𝐜𝐫𝐞𝐚𝐬𝐞𝐝 𝐦𝐞𝐭𝐚𝐥 𝐢𝐧𝐭𝐨𝐱𝐢𝐜𝐚𝐭𝐢𝐨𝐧 𝐢𝐧 𝐭𝐡𝐞𝐬𝐞 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬?
If there is increased expression of MTs due to elevated intracellular zinc levels, as described in the model, those MTs will be busy binding and regulating zinc and, potentially, copper. As a result, there would be fewer MTs available to bind and detoxify heavy metals that may be present. This could lead to an accumulation of unregulated and potentially toxic heavy metals (such as cadmium and mercury) in the body.

𝐃𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐦𝐨𝐝𝐞𝐥 𝐞𝐱𝐩𝐥𝐚𝐢𝐧 𝐭𝐡𝐞 𝐢𝐧𝐜𝐫𝐞𝐚𝐬𝐞𝐝 𝐨𝐱𝐢𝐝𝐚𝐭𝐢𝐯𝐞 𝐬𝐭𝐫𝐞𝐬𝐬 𝐢𝐧 𝐭𝐡𝐞𝐬𝐞 𝐝𝐢𝐬𝐞𝐚𝐬𝐞𝐬?
Yes, the model explains the increased oxidative stress. Infected ectopic lymphoid structures trigger inflammatory responses by releasing certain viral components. This activation induces the release of proinflammatory cytokines, which, in turn, promote excessive production of reactive oxygen species, leading to marked oxidative stress. In addition, perturbation in the homeostasis of certain metals contributes to the disruption of intracellular antioxidant responses. Specifically, there is evidence that an antioxidant enzyme (superoxide dismutase) is affected by altered copper and zinc concentration. Briefly, the model describes how the combination of chronic inflammatory responses, together with imbalances in the homeostasis of certain metals and the persistent release of proinflammatory agents, culminates in a significant increase in oxidative and nitrosative stress in the body.

𝐃𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐦𝐨𝐝𝐞𝐥 𝐞𝐱𝐩𝐥𝐚𝐢𝐧 𝐞𝐱𝐞𝐫𝐜𝐢𝐬𝐞 𝐢𝐧𝐭𝐨𝐥𝐞𝐫𝐚𝐧𝐜𝐞 𝐚𝐧𝐝 𝐩𝐨𝐬𝐭-𝐞𝐱𝐞𝐫𝐭𝐢𝐨𝐧𝐚𝐥 𝐦𝐚𝐥𝐚𝐢𝐬𝐞?
Yes, this model explains exercise intolerance and post-exertional distress in the context of persistent EBV infection and its metabolic, immunological and neurophysiological interactions. The following is a breakdown of how the model addresses this phenomenon:

1️⃣ 𝐌𝐞𝐭𝐚𝐛𝐨𝐥𝐢𝐜 𝐚𝐥𝐭𝐞𝐫𝐚𝐭𝐢𝐨𝐧𝐬: the model describes how EBV infection can lead to insulin resistance through elevated IFN-γ production. This resistance, accompanied by compensatory hyperinsulinemia, can lead to transient hypoglycemia and decreased peripheral tissue metabolism. These factors contribute to exercise intolerance, as muscles are unable to obtain the necessary energy efficiently, resulting in early fatigue.

2️⃣ 𝐀𝐥𝐭𝐞𝐫𝐚𝐭𝐢𝐨𝐧𝐬 𝐢𝐧 𝐜𝐚𝐫𝐝𝐢𝐨𝐯𝐚𝐬𝐜𝐮𝐥𝐚𝐫 𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧: High levels of serotonin and activation of certain receptors, such as TLR3 and TLR2, can alter cardiovascular function, affecting blood distribution and the body's ability to meet oxygen demands during exercise.

3️⃣ 𝐂𝐨𝐦𝐩𝐫𝐨𝐦𝐢𝐬𝐞𝐝 𝐭𝐡𝐞𝐫𝐦𝐨𝐫𝐞𝐠𝐮𝐥𝐚𝐭𝐢𝐨𝐧: The body's ability to dissipate heat generated during exercise may be impaired, which could lead to overheating.

4️⃣ 𝐎𝐱𝐢𝐝𝐚𝐭𝐢𝐯𝐞 𝐬𝐭𝐫𝐞𝐬𝐬: Chronic infection with EBV generates constant oxidative stress, which can impair mitochondrial function and reduce the ability of muscle tissue to generate energy efficiently. This oxidative stress exacerbated during exercise can lead to cell damage and muscle fatigue.

5️⃣ 𝐀𝐥𝐭𝐞𝐫𝐚𝐭𝐢𝐨𝐧𝐬 𝐢𝐧 𝐫𝐞𝐬𝐩𝐢𝐫𝐚𝐭𝐨𝐫𝐲 𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧: Respiratory function may be impaired, limiting adequate oxygenation during exercise and contributing to fatigue.

6️⃣ 𝐒𝐲𝐬𝐭𝐞𝐦𝐢𝐜 𝐢𝐧𝐟𝐥𝐚𝐦𝐦𝐚𝐭𝐢𝐨𝐧: Activation of certain receptors, release of proinflammatory cytokines and other mechanisms associated with chronic infection can generate systemic inflammation. This inflammation can negatively affect the body's ability to recover after exercise, contributing to post-exertional malaise.

7️⃣ 𝐀𝐥𝐭𝐞𝐫𝐚𝐭𝐢𝐨𝐧𝐬 𝐢𝐧 𝐧𝐞𝐮𝐫𝐨𝐥𝐨𝐠𝐢𝐜𝐚𝐥 𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧: Metabolic changes and systemic inflammation can have an impact on the central nervous system. Reduced serotonin availability and other alterations may contribute to feelings of fatigue and lethargy.

𝐃𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐦𝐨𝐝𝐞𝐥 𝐞𝐱𝐩𝐥𝐚𝐢𝐧 𝐭𝐡𝐞 𝐝𝐲𝐬𝐚𝐮𝐭𝐨𝐧𝐨𝐦𝐢𝐚 𝐩𝐫𝐞𝐬𝐞𝐧𝐭 𝐢𝐧 𝐭𝐡𝐞𝐬𝐞 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬?
Yes, here is a breakdown of how the model can generate dysautonomia:

1️⃣ 𝐄𝐁𝐕 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧: the inability to adequately control EBV latency I cells could result in chronic inflammatory responses, which disrupts immune system homeostasis and, by extension, affects the autonomic nervous system (ANS).

2️⃣ 𝐈𝐧𝐟𝐥𝐚𝐦𝐦𝐚𝐭𝐨𝐫𝐲 𝐫𝐞𝐬𝐩𝐨𝐧𝐬𝐞𝐬: proinflammatory cytokines released in response to EBV, such as IL-1β, IL-6 and TNF-α, can act on the brain and other organs, disrupting ANS function, leading to symptoms of dysautonomia.

3️⃣ 𝐌𝐞𝐭𝐚𝐛𝐨𝐥𝐢𝐜 𝐚𝐥𝐭𝐞𝐫𝐚𝐭𝐢𝐨𝐧𝐬: Hypozincemia and alterations in copper transport can imbalance the function of key enzymes, such as DAO. Impaired DAO function leads to an accumulation of histamine, a mediator that can cause symptoms of dysautonomia, such as vasodilatation and arrhythmias.

4️⃣ 𝐆𝐚𝐬𝐭𝐫𝐨𝐢𝐧𝐭𝐞𝐬𝐭𝐢𝐧𝐚𝐥 𝐝𝐢𝐬𝐭𝐮𝐫𝐛𝐚𝐧𝐜𝐞𝐬: Serotonin accumulation in the gut can stimulate the vagus nerve, a primary connection between the gut and the brain. Overstimulation of the vagus nerve can trigger symptoms of dysautonomia, such as bradycardia.

5️⃣ 𝐍𝐞𝐮𝐫𝐨𝐥𝐨𝐠𝐢𝐜𝐚𝐥 𝐚𝐥𝐭𝐞𝐫𝐚𝐭𝐢𝐨𝐧𝐬: A decrease in brain extracellular serotonin and an increase in neurotoxic metabolites of kynurenine may alter neuronal and ANS function, which could manifest as fatigue, exercise intolerance and other symptoms of dysautonomia.

6️⃣ 𝐕𝐚𝐬𝐜𝐮𝐥𝐚𝐫 𝐚𝐥𝐭𝐞𝐫𝐚𝐭𝐢𝐨𝐧𝐬: Microclot formation can affect adequate blood perfusion in organs and tissues, including the brain. Inadequate perfusion can result in neurological and autonomic symptoms.

7️⃣ 𝐄𝐧𝐝𝐨𝐜𝐫𝐢𝐧𝐞 𝐝𝐢𝐬𝐭𝐮𝐫𝐛𝐚𝐧𝐜𝐞𝐬: Hyperinsulinemia and possible reduction in cortisol secretion may affect the balance of the ANS. For example, hypoglycemia may trigger an acute sympathetic response, while decreased cortisol may affect the body's ability to handle stress.

𝐃𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐦𝐨𝐝𝐞𝐥 𝐞𝐱𝐩𝐥𝐚𝐢𝐧 𝐧𝐞𝐮𝐫𝐨𝐢𝐧𝐟𝐥𝐚𝐦𝐦𝐚𝐭𝐢𝐨𝐧, 𝐦𝐞𝐧𝐭𝐚𝐥 𝐟𝐨𝐠 𝐚𝐧𝐝 𝐜𝐨𝐠𝐧𝐢𝐭𝐢𝐯𝐞 𝐢𝐦𝐩𝐚𝐢𝐫𝐦𝐞𝐧𝐭?
Yes, this presented model could explain neuroinflammation, mental fog and cognitive impairment as follows:

1️⃣ 𝐍𝐞𝐮𝐫𝐨𝐢𝐧𝐟𝐥𝐚𝐦𝐦𝐚𝐭𝐢𝐨𝐧: In patients with ME/CFS and LC, there is evidence of chronic viral infection or virus reactivation, especially EBV. When viral genetic material is present, especially EBV EBERs, TLR3 receptors in microglia (immune cells of the central nervous system) are activated. This activation results in the release of proinflammatory cytokines such as IL-1β and TNF-α. These cytokines may contribute to chronic inflammation of the central nervous system, characterizing neuroinflammation.

2️⃣ 𝐌𝐞𝐧𝐭𝐚𝐥 𝐟𝐨𝐠 𝐚𝐧𝐝 𝐜𝐨𝐠𝐧𝐢𝐭𝐢𝐯𝐞 𝐢𝐦𝐩𝐚𝐢𝐫𝐦𝐞𝐧𝐭: several pathways mentioned in the model may contribute to these symptoms. For example:

- Viral infection can cause damage to the blood-brain barrier, allowing entry of viral genetic material that could further activate microglia and contribute to neuroinflammation.

- Increased IDO activity and decreased tryptophan levels lead to a reduction in serotonin (5-HT) and melatonin synthesis. Since serotonin plays a role in the regulation of mood, cognition and alertness, its reduction could contribute to mental fog.

- Quinolinic acid, a metabolite of tryptophan, has neurotoxic properties by binding to the NMDA receptor, which may increase nitrosative stress and contribute to cognitive impairment.

- Increased oxidative and nitrosative stress in EBV-infected cells, together with neuroinflammation, may interfere with proper neuronal functioning and contribute to cognitive impairment.

- Alterations in the serotonergic system may also directly affect cognitive function and perception of fatigue.

𝐋𝐢𝐧𝐤:

𝐂𝐨𝐧𝐭𝐢𝐧𝐮𝐞 𝐭𝐡𝐞 𝐭𝐡𝐫𝐞𝐚𝐝 🧵👇🏽

#EpsteinBarrVirus #EBV #LongCovid #MECFS #MyalgicEncephalomyelitis #Health #Research #News #microE2324 #medicine #Microbiology #VIRUS #ChronicDiseases #SARSCOV2 #COVID19 #LongHaulers #MCAS #ME #MyE #CFSME

@microbeminded2 @MVGutierrezMD @elisaperego78 @TomKindlon @Dan_Wyke @research_long @agy_lena @SarahOC_MECFS @joshuamcclure @Lymenews @JanetDafoe @EricTopol
@SGriffin_Lab
𝐃𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐦𝐨𝐝𝐞𝐥 𝐞𝐱𝐩𝐥𝐚𝐢𝐧 𝐭𝐡𝐞 𝐨𝐜𝐜𝐮𝐫𝐫𝐞𝐧𝐜𝐞 𝐨𝐟 𝐝𝐢𝐠𝐞𝐬𝐭𝐢𝐯𝐞 𝐩𝐫𝐨𝐛𝐥𝐞𝐦𝐬, 𝐟𝐨𝐨𝐝 𝐢𝐧𝐭𝐨𝐥𝐞𝐫𝐚𝐧𝐜𝐞𝐬 𝐚𝐧𝐝 𝐚𝐥𝐭𝐞𝐫𝐚𝐭𝐢𝐨𝐧𝐬 𝐢𝐧 𝐭𝐡𝐞 𝐦𝐢𝐜𝐫𝐨𝐛𝐢𝐨𝐭𝐚 𝐢𝐧 𝐭𝐡𝐞𝐬𝐞 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬?
Yes, I will summarize the key points below:

1️⃣ 𝐃𝐢𝐠𝐞𝐬𝐭𝐢𝐯𝐞 𝐩𝐫𝐨𝐛𝐥𝐞𝐦𝐬:
- The accumulation of 5-HT (serotonin) in the intestinal mucosa causes chronic inflammation.

- This intestinal inflammation leads to a decrease in stomach acid secretion and in the expression of enzymes needed to digest carbohydrates. As a result, more carbohydrates reach the intestinal microbiota without being digested or absorbed, which can cause digestive problems such as bloating, gas and diarrhea.

- The serotonergic alteration, together with the increase in proinflammatory cytokines, causes an alteration in acid secretion, breakdown of the intestinal barrier and decreased expression of enzymes needed to digest carbohydrates.

2️⃣ 𝐅𝐨𝐨𝐝 𝐢𝐧𝐭𝐨𝐥𝐞𝐫𝐚𝐧𝐜𝐞𝐬:
- Dysfunction of adaptive immunity, combined with increased nutrient input for commensal bacteria and decreased acid secretion, leads to bacterial proliferation, resulting in small intestinal bacterial overgrowth (SIBO) and the development of food intolerances.

- Alterations in the intestinal barrier allow substances and microorganisms that should not normally cross it to do so, further activating innate immunity and leading to increased accumulation of 5-HT, which aggravates symptoms.

3️⃣ 𝐀𝐥𝐭𝐞𝐫𝐚𝐭𝐢𝐨𝐧𝐬 𝐢𝐧 𝐭𝐡𝐞 𝐦𝐢𝐜𝐫𝐨𝐛𝐢𝐨𝐭𝐚:
- The disruption of tight junctions between enterocytes, caused by increased proinflammatory cytokines, leads to increased intestinal permeability. As a result, bacteria and substances that should not cross the barrier do so, which alters the microbiota and leads to increased activation of the innate immune system.

- SIBO has other consequences, such as bacterial deconjugation of bile salts, leading to poor micelle formation and fat malabsorption, as well as deficiencies in fat-soluble vitamins (A, D, E, and K). In addition, competitive absorption of vitamin B12 by bacteria results in less binding to intrinsic factor and, therefore, less absorption in the terminal ileum.

𝐃𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐦𝐨𝐝𝐞𝐥 𝐞𝐱𝐩𝐥𝐚𝐢𝐧 𝐭𝐡𝐞 𝐦𝐞𝐭𝐚𝐛𝐨𝐥𝐢𝐜 𝐚𝐥𝐭𝐞𝐫𝐚𝐭𝐢𝐨𝐧𝐬 𝐚𝐧𝐝 𝐦𝐢𝐭𝐨𝐜𝐡𝐨𝐧𝐝𝐫𝐢𝐚𝐥 𝐝𝐲𝐬𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧 𝐩𝐫𝐞𝐬𝐞𝐧𝐭 𝐢𝐧 𝐭𝐡𝐞𝐬𝐞 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬?
Yes, let's see how:

1️⃣ 𝐌𝐞𝐭𝐚𝐛𝐨𝐥𝐢𝐜 𝐚𝐥𝐭𝐞𝐫𝐚𝐭𝐢𝐨𝐧𝐬:
- EBV infection, especially in individuals with "weak" HLA-II haplotypes, leads to immune evasion, which promotes inflammatory responses in the body. This inflammation can affect various metabolic pathways.

- Increased release of proinflammatory cytokines, such as IL-1β, IL-6, IL-8, IL-12, TNF-α, and IFN-γ, has metabolic consequences. These cytokines can alter the balance of certain minerals such as zinc and copper, which can disrupt several essential enzymatic functions.

- Insulin resistance induced by elevated levels of IFN-γ affects glucose metabolism. To compensate, the pancreas produces more insulin, leading to hyperinsulinemia, which has various consequences, including an effect on hepatic glycogen metabolism.

2️⃣ 𝐌𝐢𝐭𝐨𝐜𝐡𝐨𝐧𝐝𝐫𝐢𝐚𝐥 𝐝𝐲𝐬𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧:
- Serotonergic disturbances caused by infections can affect mitochondrial function. Serotonin depletion in the central nervous system (CNS) plays a role in the regulation of appetite and energy metabolism.

- Constant activation of the anaerobic glycolytic pathway, either due to the Warburg effect in infected cells or due to mitochondrial dysfunction, results in elevated lactic acid production.

- The generation of quinolinic, a metabolite of tryptophan, may be neurotoxic and contribute to nitrosative stress, which may further impair mitochondrial function.

- Overstimulation of NMDA receptors, whether by quinolinic acid or other pathways, can lead to increased nitric oxide/peroxynitrite levels, which has direct consequences on mitochondrial function and health.

3️⃣ 𝐆𝐥𝐨𝐛𝐚𝐥 𝐜𝐨𝐧𝐬𝐞𝐪𝐮𝐞𝐧𝐜𝐞𝐬:
- Energy depletion, as a result of metabolic alterations and mitochondrial dysfunction, can manifest as chronic fatigue and other associated symptoms.

- Alterations in the serotonergic system, along with metabolic imbalances and chronic inflammation, may contribute to neurological symptoms, including fatigue and depression.

𝐃𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐦𝐨𝐝𝐞𝐥 𝐞𝐱𝐩𝐥𝐚𝐢𝐧 𝐭𝐡𝐞 𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐦𝐢𝐜𝐫𝐨𝐜𝐥𝐨𝐭 𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧?
Yes, the following are the key points of this process according to the model:

1️⃣ 𝐏𝐫𝐨𝐢𝐧𝐟𝐥𝐚𝐦𝐦𝐚𝐭𝐨𝐫𝐲 𝐜𝐲𝐭𝐨𝐤𝐢𝐧𝐞𝐬 𝐚𝐧𝐝 𝐡𝐲𝐩𝐞𝐫𝐜𝐨𝐚𝐠𝐮𝐥𝐚𝐭𝐢𝐨𝐧:
- Overproduction of proinflammatory cytokines, such as TNFα, IL-6 and IL-1β during infectious processes, leads to hypercoagulation, platelet activation, leukocyte infiltration and vascular hyperpermeability.

2️⃣ 𝐏𝐥𝐚𝐭𝐞𝐥𝐞𝐭 𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧:
- Platelets, when activated through 5-HT2A receptors due to increased 5-HT in peripheral blood or by binding of EBERs to TLR3, bind fibrinogen, which enhances aggregation and coagulation processes.

- Activated platelets can release β-amyloid (Aβ) peptide, which, interacting with fibrinogen, causes fibrinogen oligomerization, fibrin deposition and Aβ fibrillation, favoring the formation of abnormal microclots resistant to degradation by fibrinolytic enzymes.

3️⃣ 𝐀𝐦𝐲𝐥𝐨𝐢𝐝𝐨𝐠𝐞𝐧𝐞𝐬𝐢𝐬 𝐚𝐧𝐝 𝐟𝐢𝐛𝐫𝐢𝐧𝐨𝐠𝐞𝐧𝐞𝐬𝐢𝐬:
- Elevated levels of IL-1β, IL-6 and TNF-α stimulate the production of serum amyloid A (SAA) protein in hepatocytes.

- Increased SAA in the blood may favor its interaction with fibrinogen, leading to amyloidogenic changes in fibrinogen, resulting in the formation of fibrin amyloid microaggregates resistant to fibrinolysis.

4️⃣ 𝐂𝐚𝐩𝐢𝐥𝐥𝐚𝐫𝐲 𝐨𝐛𝐬𝐭𝐫𝐮𝐜𝐭𝐢𝐨𝐧 𝐚𝐧𝐝 𝐞𝐧𝐝𝐨𝐭𝐡𝐞𝐥𝐢𝐚𝐥 𝐝𝐚𝐦𝐚𝐠𝐞:
- The formation of these micro-clots leads to capillary obstruction, which compromises blood flow and increases inflammation, contributing to the appearance of various symptoms.

- In addition, endothelial damage caused by EBV infection, either through positive activation of NOX2 by EBNA-1 in EBV-transformed endothelial cells or through activation of TLR3 by EBERs, may influence microclot formation. NOX2 activation may cause vasoconstriction and thrombosis through platelet aggregation via overproduction of hydrogen peroxide, isoprostanes, or inactivation of nitric oxide.

𝐃𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐦𝐨𝐝𝐞𝐥 𝐞𝐱𝐩𝐥𝐚𝐢𝐧 𝐭𝐡𝐞 𝐚𝐥𝐭𝐞𝐫𝐚𝐭𝐢𝐨𝐧 𝐢𝐧 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥 𝐥𝐞𝐯𝐞𝐥𝐬?
Yes. The following are the key points of this process according to the model:

1️⃣ 𝐈𝐧𝐢𝐭𝐢𝐚𝐥 𝐬𝐭𝐢𝐦𝐮𝐥𝐮𝐬:
- Under acute conditions, proinflammatory cytokines such as IFN-γ, TNFα, IL-1 and IL-6 stimulate the hypothalamic-pituitary-adrenal (HPA) axis by activating ACTH secretion. IFN-γ, for example, not only activates macrophages, but also allows an increase in glucocorticoid receptor expression for subsequent feedback inhibition. So that the inflammatory response is not exaggerated, there is a stimulation in cortisol secretion due to the increase in ACTH, which results from the action of IFN-γ and the direct stimulation of the adrenal gland by IL-6.

2️⃣ 𝐒𝐮𝐩𝐩𝐫𝐞𝐬𝐬𝐢𝐨𝐧 𝐨𝐟 𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥 𝐬𝐞𝐜𝐫𝐞𝐭𝐢𝐨𝐧 𝐝𝐮𝐫𝐢𝐧𝐠 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧𝐬:
- During persistent infections, chronic exposure to IL-10, TGF-β1 and TNFα could suppress ACTH-stimulated cortisol secretion in the adrenal gland, leading to relative hypocortisolism.

- The anti-inflammatory and immunosuppressive cytokines, IL-10 and TGF-β1, are elevated in EBV infections. These cytokines are secreted by EBV latent cells and regulatory T cells to counteract proinflammatory cytokines and evade CD4 T cells. Therefore, the greater the number of EBV reservoir-infected tissues, the greater the secretion of these anti-inflammatory cytokines and thus the greater the negative feedback on cortisol secretion.

3️⃣ 𝐏𝐨𝐬𝐬𝐢𝐛𝐥𝐞 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧 𝐢𝐧 𝐭𝐡𝐞 𝐚𝐝𝐫𝐞𝐧𝐚𝐥 𝐨𝐫 𝐩𝐢𝐭𝐮𝐢𝐭𝐚𝐫𝐲 𝐠𝐥𝐚𝐧𝐝𝐬:
- Disease progression and acquired immunodeficiency in CD4 T-cell function may lead to an increase in the replicative rate of the virus and infection in the adrenal or pituitary glands, depleting cortisol stores.

4️⃣ 𝐈𝐦𝐩𝐚𝐜𝐭 𝐨𝐟 𝐜𝐡𝐫𝐨𝐧𝐢𝐜 𝐢𝐧𝐬𝐮𝐥𝐢𝐧𝐢𝐬𝐦:
- Chronic high insulin may also play a role in the development of hypocortisolism, as insulin may inhibit the secretion of corticotropin-releasing hormone in the hypothalamus, which in turn would inhibit ACTH secretion in the pituitary gland.

🔵In the next days I will be uploading more consequences that our model responds. As a patient with ME/CFS after EBV infection, I see the urgent need to find treatments against this virus.
#Science #virology #Immunology

🦠 🔍 ¿𝐒𝐚𝐛𝐢́𝐚𝐬 𝐪𝐮𝐞 𝐞𝐥 𝐯𝐢𝐫𝐮𝐬 𝐝𝐞 𝐄𝐩𝐬𝐭𝐞𝐢𝐧-𝐁𝐚𝐫𝐫 𝐩𝐨𝐝𝐫𝐢́𝐚 𝐬𝐞𝐫 𝐮𝐧 𝐝𝐞𝐬𝐞𝐧𝐜𝐚𝐝𝐞𝐧𝐚𝐧𝐭𝐞 𝐝𝐞 𝐥𝐨𝐬 𝐬𝐢́𝐧𝐭𝐨𝐦𝐚𝐬 𝐞𝐧 𝐥𝐚 𝐄𝐌/𝐒𝐅𝐂 𝐲 𝐞𝐧 𝐞𝐥 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃? Abro 🧵

A continuación, os resumo los puntos de nuestra reciente revisión publicada y como podría explicar el desarrollo de 𝐝𝐢𝐬𝐚𝐮𝐭𝐨𝐧𝐨𝐦𝐢́𝐚, 𝐦𝐢𝐜𝐫𝐨𝐜𝐨𝐚́𝐠𝐮𝐥𝐨𝐬, 𝐞𝐧𝐟𝐞𝐫𝐦𝐞𝐝𝐚𝐝𝐞𝐬 𝐚𝐮𝐭𝐨𝐢𝐧𝐦𝐮𝐧𝐞𝐬, 𝐢𝐧𝐭𝐨𝐥𝐞𝐫𝐚𝐧𝐜𝐢𝐚 𝐚𝐥 𝐞𝐣𝐞𝐫𝐜𝐢𝐜𝐢𝐨, 𝐝𝐢𝐬𝐟𝐮𝐧𝐜𝐢𝐨́𝐧 𝐦𝐢𝐭𝐨𝐜𝐨𝐧𝐝𝐫𝐢𝐚𝐥, 𝐡𝐢𝐩𝐨𝐜𝐨𝐫𝐭𝐢𝐬𝐨𝐥𝐢𝐬𝐦𝐨 𝐲 𝐦𝐮𝐜𝐡𝐚𝐬 𝐦𝐚́𝐬 𝐜𝐨𝐧𝐬𝐞𝐜𝐮𝐞𝐧𝐜𝐢𝐚𝐬.

Muchos se preguntan por qué el EBV, el virus de Epstein-Barr, y no otro virus, es el principal desencadenante del cuadro sintomático de la EM/SFC y del Long COVID, cuando existen otros factores, como distintas infecciones, intoxicación por metales, entre otros. En las siguientes líneas, expondré los fundamentos de este fenómeno, resumiendo los puntos esenciales del artículo de revisión que publicamos recientemente.

El común denominador de todos los factores desencadenantes de ambas enfermedades es su capacidad para inmunodeprimir. Toda infección intracelular, sea bacteriana, viral o parasitaria, que no sea controlada, lleva a la inmunosupresión debido a la exposición crónica a antígenos. Normalmente, la habilidad para controlar una infección se debe a factores genéticos, particularmente a los genes HLA (I y II). Estos genes codifican proteínas llamadas antígeno leucocitario humano (HLA), esenciales para distinguir lo propio de lo ajeno en nuestro cuerpo. Si esta "alerta" no funciona adecuadamente, el sistema inmune no puede eliminar eficientemente patógenos. Los HLA son como un escáner que permite identificar las cosas que no son del cuerpo y responder a ellas. Si este escáner no funciona correctamente y no reconoce algo que es malo, impediría que tu sistema inmune lo elimine y por tanto, que se mueva libremente por tu organismo sin ser eliminado.

En el contexto de la EM/SFC, existen 𝐝𝐨𝐬 𝐞𝐬𝐜𝐞𝐧𝐚𝐫𝐢𝐨𝐬 𝐩𝐨𝐬𝐢𝐛𝐥𝐞𝐬: el individuo puede tener una predisposición genética directa frente al EBV, o puede perder el control sobre el EBV debido a una inmunodeficiencia subyacente causada por otra infección o exposición a químicos o metales. Si se trata de otra infección, también estaríamos hablando de una "debilidad genética" (HLA) frente a esos patógenos específicos.

Si el individuo es genéticamente susceptible al EBV, es porque posee haplotipos HLA-II antiguos, a los que el EBV ha coevolucionado. Esto se debe principalmente porque el EBV infecta uniéndose a las proteinas HLA-II de las células. Este virus es astuto: al infectar una célula, introduce su ADN en ella de manera latente sin generar nuevos viriones, evitando la detección del sistema inmune y utilizando las células B como "caballos de Troya".

Si bien el 95% de la población mundial tiene EBV, solo una minoría desarrolla problemas. Aquí es donde entran en juego de nuevo los haplotipos HLA-II “débiles” frente al EBV.

Aunque se diga que la mayoría de la población no tiene problemas con este virus, eso no del todo cierto. Pensad que este virus se aprovecha cada vez que os inmunodeprimís por cualquier motivo. Un ejemplo lo tenéis con su hermano herpes labial, que cada vez que esa persona se inmunodeprime por cualquier motivo, aprovecha e infecta más células haciendose visible la lesión en los labios. Pero cada vez que vuelve a remontar el sistema inmunologico del primer evento que lo inmunodeprimió, se vuelve a controlar este virus y desaparece la lesión. Esto es exactamente lo mismo que ocurre en las personas sanas que son capaces de controlar el EBV.

La principal diferencia entre estas personas sanas y los pacientes de EM/SFC que tienen problemas con el EBV, es que al tener haplotipos HLA-II fuertes contra el EBV son capaces de reconocer todos los tipos de latencia del EBV y controlarlos. En cambio, 𝐥𝐨𝐬 𝐩𝐚𝐜𝐢𝐞𝐧𝐭𝐞𝐬 𝐜𝐨𝐧 𝐄𝐌/𝐒𝐅𝐂 𝐩𝐨𝐫 𝐄𝐁𝐕, 𝐚𝐥 𝐭𝐞𝐧𝐞𝐫 𝐡𝐚𝐩𝐥𝐨𝐭𝐢𝐩𝐨𝐬 𝐝𝐞́𝐛𝐢𝐥𝐞𝐬 𝐜𝐨𝐧𝐭𝐫𝐚 𝐞𝐥 𝐄𝐁𝐕, 𝐬𝐮𝐬 𝐜𝐞́𝐥𝐮𝐥𝐚𝐬 𝐓𝐂𝐃𝟒 𝐧𝐨 𝐬𝐨𝐧 𝐜𝐚𝐩𝐚𝐜𝐞𝐬 𝐝𝐞 𝐫𝐞𝐜𝐨𝐧𝐨𝐜𝐞𝐫 𝐥𝐚𝐬 𝐜𝐞́𝐥𝐮𝐥𝐚𝐬 𝐜𝐨𝐧 𝐥𝐚𝐭𝐞𝐧𝐜𝐢𝐚 𝐈 𝐝𝐞𝐥 𝐄𝐁𝐕. El resto de tipos de latencias si son capaces de ser reconocidas puesto que son controladas por las células TCD8, ya que no tendrían haplotipos HLA-I débiles contra el EBV.

Vamos a explicar mejor esto. Las células TCD4 reconocen antígenos presentados en proteínas HLA-II y las células TCD8 reconocen antígenos presentados en proteínas HLA-I. Normalmente, cualquier infección intracelular es controlada por las células TCD8 porque las células infectadas presentan en las proteínas HLA-I de su membrana los antígenos del patógeno que tienen dentro. Por otro lado, las proteínas HLA-II se encuentran sobre todo en células presentadoras de antígenos que se encargan de coger antígenos que se encuentran fuera de la célula y presentarlos en sus proteínas HLA-II para que sean reconocidas por las células T-CD4. Entonces, pensaríamos que el EBV al ser un patógeno intracelular, sus antígenos deberían ser presentados siempre en las proteínas HLA-I de la célula infectada. Pues esto no es así siempre, este virus ha evolucionado para esquivar este sistema al generar latencia. Uno de los mecanismos de evasión para permanecer sin ser reconocido es evitar que un antígeno de latencia, llamado EBNA-1, sea presentado en las proteínas HLA-I y pase a ser presentado en las HLA-II. Esto es de suma importancia para el virus porque evita por ejemplo, que las células de latencia I (solo expresan EBNA-1 del virus) sean reconocidas por las células TCD8. En cambio, el resto de las células con latencia (II y III) y células líticas sin serían reconocidas y eliminadas por las células T CD8. Entonces pensaríamos que nadie podría controlar las células con latencia I si evaden a las células T CD8. Aquí nuestro sistema inmune también es inteligente y es donde las células T CD4 juegan el papel diferencial entre las personas sanas y enfermas con este virus. Vuelve a aparecer la importancia de los haplotipos HLA-II. Aquellos individuos que tengan haplotipos HLA-II resistentes al EBV serán capaces de presentar bien el antígeno EBNA-1 en las células con latencia I y serán reconocidas y eliminadas por las células TCD4. En cambio, aquellos que tengan los haplotipos HLA-II débiles frente al EBV, no podrán presentar bien EBNA-1 en las proteínas HLA-II y por tanto, las células T CD4 no reconocerán las células con latencia I. Estas células con latencia I al no ser controladas, se multiplicarán y causarán inflamación y daño. Pero cada vez que pasen a otro tipo de latencia o a fase lítica si serán reconocidas por las células T CD8.

Entonces ¿𝐪𝐮𝐞́ 𝐨𝐜𝐮𝐫𝐫𝐞 𝐜𝐨𝐧 𝐚𝐪𝐮𝐞𝐥𝐥𝐨𝐬 𝐢𝐧𝐝𝐢𝐯𝐢𝐝𝐮𝐨𝐬 𝐪𝐮𝐞 𝐬𝐞 𝐡𝐚𝐧 𝐢𝐧𝐟𝐞𝐜𝐭𝐚𝐝𝐨 𝐜𝐨𝐧 𝐨𝐭𝐫𝐨𝐬 𝐩𝐚𝐭𝐨́𝐠𝐞𝐧𝐨𝐬 (𝐜𝐨𝐦𝐨 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃) 𝐲 𝐧𝐨 𝐥𝐨𝐠𝐫𝐚𝐧 𝐜𝐨𝐧𝐭𝐫𝐨𝐥𝐚𝐫𝐥𝐨𝐬? Pues al final ocurre lo mismo. Al ser débiles genéticamente contra estos patógenos acaban también presentando una inmunodeficiencia por la exposición crónica a los antígenos, disminuyendo la respuesta efectiva de las células T CD4. Como estas células son las principales que controlan la latencia I del EBV, las células con latencia I acaban evadiendo al sistema inmune y multiplicándose, generando los mismos problemas que en el caso de la EM/SFC por EBV.

Por tanto, en cualquier subtipo de paciente con EM/SFC y en el Long COVID, acaban presentando un síndrome viral por el EBV. Una vez instaurado el descontrol de las células con latencia I de EBV, permite que cualquier estímulo inflamatorio en cualquier tejido reclute leucocitos (entre los cuales se encuentran células con latencia del VEB), lo que en última instancia conduce a la 𝐟𝐨𝐫𝐦𝐚𝐜𝐢𝐨́𝐧 𝐝𝐞 𝐚𝐠𝐫𝐞𝐠𝐚𝐝𝐨𝐬 𝐥𝐢𝐧𝐟𝐨𝐢𝐝𝐞𝐬 𝐞𝐜𝐭𝐨́𝐩𝐢𝐜𝐨𝐬 𝐢𝐧𝐟𝐞𝐜𝐭𝐚𝐝𝐚𝐬 𝐩𝐨𝐫 𝐞𝐥 𝐕𝐄𝐁.

Estas formaciones son "ectópicas" porque se encuentran fuera de su ubicación habitual, es decir, no se forman en los tejidos linfoides primarios (como el timo y la médula ósea) o secundarios (como los ganglios linfáticos y el bazo). Se forman de manera transitoria para hacer frente a una infección o inflamación y desaparecen cuando se resuelve el estímulo.

Las células B con latencia de EBV usan estos agregados linfoides en su beneficio, ya que como hay presentación de antígenos en estas estructuras, lo aprovechan para pasar de formas de latencia a fase lítica, generando focos de reactivaciones virales en estos tejidos inflamados. Esto hace que, aunque se haya resuelto el estímulo inflamatorio inicial que provocó la formación de estos agregados, permanezcan continuamente estos agregados en estos tejidos al permanecer otro estímulo inflamatorio debido tanto a las moléculas liberadas por las células con latencia, como las reactivaciones virales. Esto ocurriría sobre todo en las mucosas de nuestro organismo pero puede ocurrir en diferentes tejidos y sería la base del 𝐝𝐞𝐬𝐚𝐫𝐫𝐨𝐥𝐥𝐨 𝐝𝐞 𝐥𝐚𝐬 𝐞𝐧𝐟𝐞𝐫𝐦𝐞𝐝𝐚𝐝𝐞𝐬 𝐚𝐮𝐭𝐨𝐢𝐧𝐦𝐮𝐧𝐞𝐬.

Estas enfermedades autoinmunes se generan debido a la presentación de autoantígenos celulares de esos tejidos o por la presentación de EBNA-1 viral a través de las proteínas HLA-II. Los antígenos cuando son presentados en las proteínas HLA-II sufren una serie de modificaciones que pueden provocar la formación de nuevos antígenos “diferentes” de los anteriores. Además, EBNA-1 tiene una secuencia parecida a diferentes proteínas de nuestro cuerpo, pudiendo confundir a nuestro sistema inmune y generar una respuesta autoinmune. Aquí vuelve a aparecer la implicación de tener unos haplotipos HLA-II débiles contra el EBV, ya que la mayoría de las enfermedades asociadas a este virus como la esclerosis múltiple, lupus, artritis reumatoide, Sjögren, etc están asociados a los mismos haplotipos antiguos HLA-II que los débiles frente al EBV. Por lo que tener estas enfermedades autoinmunes lleva implícito que no controlan bien estas células con latencia de EBV y por lo tanto, son las responsables del desarrollo de su autoinmunidad.

¿𝐏𝐨𝐫 𝐪𝐮𝐞́ 𝐥𝐚𝐬 𝐦𝐮𝐣𝐞𝐫𝐞𝐬 𝐩𝐫𝐞𝐬𝐞𝐧𝐭𝐚𝐧 𝐮𝐧𝐚 𝐦𝐚𝐲𝐨𝐫 𝐩𝐫𝐞𝐯𝐚𝐥𝐞𝐧𝐜𝐢𝐚 𝐝𝐞 𝐄𝐌/𝐒𝐅𝐂, 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐲 𝐞𝐧𝐟𝐞𝐫𝐦𝐞𝐝𝐚𝐝𝐞𝐬 𝐚𝐮𝐭𝐨𝐢𝐧𝐦𝐮𝐧𝐞𝐬?
Las hormonas desempeñan un papel crucial. Los estrógenos, en particular, afectan la proporción de linfocitos T CD4/CD8 al reducirla, incrementan la longevidad de las células B, potencian la liberación de anticuerpos y amplifican la expresión de las proteínas HLA-II. En condiciones normales, este incremento en los niveles de anticuerpos en las mujeres potencia su resistencia frente a infecciones virales. Sin embargo, bajo circunstancias patológicas, este equilibrio hormonal conduce a una prolongada supervivencia de las células B y a una disminución en las células T CD4, además de intensificar la expresión del HLA-II. Esta situación propicia una mayor vulnerabilidad frente al EBV debido al aumento de la supervivencia de las células B transformadas por el virus y a la mayor expresión del HLA-II, lo que facilita la infección de un mayor número de células. Sumado a esto, la elevada expresión de HLA-II puede llevar a una presentación más robusta de autoantígenos celulares o antígenos virales que, tras sufrir cambios post-traduccionales, generan neoantígenos. Estos pueden activar células autorreactivas. Por tanto, tanto el aumento de la supervivencia de las células B transformadas como el aumento de la presentación antigénica generada por el aumento de la expresión de HLA-II por el estradiol pueden favorecer un aumento en la presentación de antígenos tanto propios como extraños durante un proceso infeccioso, y aquellas células plasmáticas anormales que producen autoanticuerpos sobreviven más tiempo, lo que en consecuencia aumenta la probabilidad de que las mujeres desarrollen enfermedades autoinmunes o incluso cáncer.

Por el lado masculino, la testosterona modula el sistema inmunológico al fomentar la respuesta CD4 Th1 (antiviral) y la activación de las células T CD8, mientras que inhibe la respuesta de las células NK y la expresión del HLA-II. Dado que las células presentadoras de antígenos son esenciales para la diferenciación de las células T CD4 hacia Th1 o Th2, basándose en las citoquinas que liberan, las hormonas sexuales pueden influir en esta diferenciación. Las mujeres, al tener mayores niveles de anticuerpos (respuesta Th2), muestran una respuesta más eficiente frente a infecciones extracelulares. No obstante, frente a patógenos intracelulares, su sistema inmunológico podría no ser tan eficiente como el masculino, que se beneficia de una respuesta celular Th1 más potente para combatir células infectadas por virus.

¿𝐄𝐬𝐭𝐞 𝐦𝐨𝐝𝐞𝐥𝐨 𝐞𝐱𝐩𝐥𝐢𝐜𝐚 𝐥𝐚 𝐫𝐞𝐬𝐩𝐮𝐞𝐬𝐭𝐚 𝐢𝐧𝐦𝐮𝐧𝐞 𝐡𝐢𝐩𝐞𝐫𝐚𝐜𝐭𝐢𝐯𝐚 𝐲 𝐚 𝐥𝐚 𝐯𝐞𝐳 𝐧𝐨 𝐞𝐟𝐢𝐜𝐚𝐳?
Si, este modelo describe una situación en la que el sistema inmunológico del cuerpo está trabajando en exceso, pero de manera ineficiente, frente al virus EBV:
Respuesta adaptativa deficiente: Las células T CD4, no están reconociendo y enfrentándose correctamente a las células con latencia I del EBV. Esto lleva a que haya más células infectadas circulando y, al mismo tiempo, a una fatiga o agotamiento de las células T, reduciendo su capacidad para luchar contra el virus.

𝐒𝐨𝐛𝐫𝐞𝐚𝐜𝐭𝐢𝐯𝐚𝐜𝐢𝐨́𝐧 𝐝𝐞 𝐥𝐚 𝐢𝐧𝐦𝐮𝐧𝐢𝐝𝐚𝐝 𝐢𝐧𝐧𝐚𝐭𝐚: A causa de este fallo en la respuesta adaptativa, otra parte del sistema inmunológico, llamada inmunidad innata, se activa en exceso porque detecta continuamente que hay una infección pero que no consigue ser resuelta por la inmunidad adaptativa. Esto se traduce en la producción constante de sustancias inflamatorias que, en lugar de ayudar, pueden generar más problemas y mantener una inflamación crónica.

𝐃𝐞𝐬𝐛𝐚𝐥𝐚𝐧𝐜𝐞 𝐞𝐧 𝐥𝐚𝐬 𝐫𝐞𝐬𝐩𝐮𝐞𝐬𝐭𝐚𝐬 𝐢𝐧𝐦𝐮𝐧𝐨𝐥𝐨́𝐠𝐢𝐜𝐚𝐬: El cuerpo tiende a favorecer una respuesta inmunológica (conocida como Th2) que no es la más adecuada para combatir este tipo de infección. Esto se debe en parte a la producción de una sustancia llamada IL-6, que redirige la respuesta defensiva del cuerpo hacia la producción de anticuerpos en vez de una respuesta celular antiviral (Th1). El aumento de la respuesta Th2 favorece los ciclos de latencia y lítico del EBV al activarse más células B.

¿𝐄𝐬𝐭𝐞 𝐦𝐨𝐝𝐞𝐥𝐨 𝐞𝐱𝐩𝐥𝐢𝐜𝐚 𝐥𝐚𝐬 𝐫𝐞𝐚𝐜𝐭𝐢𝐯𝐚𝐜𝐢𝐨𝐧𝐞𝐬 𝐯𝐢𝐫𝐚𝐥𝐞𝐬 𝐲 𝐥𝐚 𝐝𝐞 𝐨𝐭𝐫𝐨𝐬 𝐩𝐚𝐭𝐨́𝐠𝐞𝐧𝐨𝐬 𝐥𝐚𝐭𝐞𝐧𝐭𝐞𝐬?
Sí, el modelo explica que, debido a la disminución en la activación y función de las células T CD4 citotóxicas, se produce una pérdida de la vigilancia inmunológica sobre las infecciones latentes de otros patógenos. Estas células T CD4 son necesarias para controlar las células con latencia o en fase lítica de patógenos como el Parvovirus B19, EBV, citomegalovirus y otros herpesvirus. Como resultado, se observará un aumento en la reactivación viral, especialmente en individuos con un grado mayor de inmunodeficiencia.

¿𝐄𝐬𝐭𝐞 𝐦𝐨𝐝𝐞𝐥𝐨 𝐞𝐱𝐩𝐥𝐢𝐜𝐚 𝐜𝐨́𝐦𝐨 𝐩𝐨𝐝𝐫𝐢́𝐚 𝐡𝐚𝐛𝐞𝐫 𝐮𝐧𝐚 𝐦𝐚𝐲𝐨𝐫 𝐢𝐧𝐭𝐨𝐱𝐢𝐜𝐚𝐜𝐢𝐨́𝐧 𝐩𝐨𝐫 𝐦𝐞𝐭𝐚𝐥𝐞𝐬 𝐞𝐧 𝐞𝐬𝐭𝐨𝐬 𝐩𝐚𝐜𝐢𝐞𝐧𝐭𝐞𝐬?
Si hay un aumento en la expresión de MTs debido a niveles elevados de zinc intracelular, como se describe en el modelo, esas MTs estarán ocupadas uniendo y regulando el zinc y, potencialmente, el cobre. Como resultado, habría menos MTs disponibles para unirse y desintoxicar los metales pesados que puedan estar presentes. Esto podría llevar a una acumulación de metales pesados (como el cadmio y el mercurio) no regulados y potencialmente tóxicos en el cuerpo.

¿𝐄𝐬𝐭𝐞 𝐦𝐨𝐝𝐞𝐥𝐨 𝐞𝐱𝐩𝐥𝐢𝐜𝐚 𝐞𝐥 𝐚𝐮𝐦𝐞𝐧𝐭𝐨 𝐝𝐞 𝐞𝐬𝐭𝐫𝐞́𝐬 𝐨𝐱𝐢𝐝𝐚𝐭𝐢𝐯𝐨 𝐞𝐧 𝐞𝐬𝐭𝐚𝐬 𝐞𝐧𝐟𝐞𝐫𝐦𝐞𝐝𝐚𝐝𝐞𝐬?
Sí, el modelo explica el aumento de estrés oxidativo. Las estructuras linfoides ectópicas infectadas desencadenan respuestas inflamatorias al liberar ciertos componentes virales. Esta activación induce a la liberación de citocinas proinflamatorias, las cuales, a su vez, fomentan la producción excesiva de especies reactivas de oxígeno, llevando a un marcado estrés oxidativo. Además, la perturbación en la homeostasis de ciertos metales contribuye a la disrupción de las respuestas antioxidantes intracelulares.
Específicamente, hay evidencia de que una enzima antioxidante (superóxido dismutasa) es afectada por la alteración en la concentración de cobre y zinc. De forma resumida, en el modelo se describe cómo la combinación de respuestas inflamatorias crónicas, junto con desequilibrios en la homeostasis de ciertos metales y la liberación persistente de agentes proinflamatorios, culmina en un aumento significativo del estrés oxidativo y nitrosativo en el cuerpo.

¿𝐄𝐬𝐭𝐞 𝐦𝐨𝐝𝐞𝐥𝐨 𝐞𝐱𝐩𝐥𝐢𝐜𝐚 𝐥𝐚 𝐢𝐧𝐭𝐨𝐥𝐞𝐫𝐚𝐧𝐜𝐢𝐚 𝐚𝐥 𝐞𝐣𝐞𝐫𝐜𝐢𝐜𝐢𝐨 𝐲 𝐞𝐥 𝐦𝐚𝐥𝐞𝐬𝐭𝐚𝐫-𝐩𝐨𝐬𝐭𝐞𝐬𝐟𝐮𝐞𝐫𝐳𝐨?
Sí, este modelo explica la intolerancia al ejercicio y el malestar-postesfuerzo en el contexto de una infección persistente por EBV y sus interacciones metabólicas, inmunológicas y neurofisiológicas. A continuación, se desglosa cómo el modelo aborda este fenómeno:

𝐀𝐥𝐭𝐞𝐫𝐚𝐜𝐢𝐨𝐧𝐞𝐬 𝐦𝐞𝐭𝐚𝐛𝐨́𝐥𝐢𝐜𝐚𝐬: El modelo describe cómo la infección por EBV puede llevar a una resistencia a la insulina a través de la producción elevada de IFN-γ. Esta resistencia, acompañada de una hiperinsulinemia compensatoria, puede conducir a una hipoglucemia transitoria y una disminución en el metabolismo de los tejidos periféricos. Estos factores contribuyen a la intolerancia al ejercicio, ya que los músculos no pueden obtener la energía necesaria de manera eficiente, resultando en fatiga temprana.

𝐀𝐥𝐭𝐞𝐫𝐚𝐜𝐢𝐨𝐧𝐞𝐬 𝐞𝐧 𝐥𝐚 𝐟𝐮𝐧𝐜𝐢𝐨́𝐧 𝐜𝐚𝐫𝐝𝐢𝐨𝐯𝐚𝐬𝐜𝐮𝐥𝐚𝐫: Los altos niveles de serotonina y la activación de ciertos receptores, como TLR3 y TLR2, pueden alterar la función cardiovascular, afectando la distribución de sangre y la capacidad del cuerpo para satisfacer las demandas de oxígeno durante el ejercicio.

𝐓𝐞𝐫𝐦𝐨𝐫𝐫𝐞𝐠𝐮𝐥𝐚𝐜𝐢𝐨́𝐧 𝐜𝐨𝐦𝐩𝐫𝐨𝐦𝐞𝐭𝐢𝐝𝐚: La capacidad del cuerpo para disipar el calor generado durante el ejercicio puede verse afectada, lo que podría llevar a un sobrecalentamiento.

𝐄𝐬𝐭𝐫𝐞́𝐬 𝐨𝐱𝐢𝐝𝐚𝐭𝐢𝐯𝐨: La infección crónica con EBV genera un constante estrés oxidativo, que puede deteriorar la función mitocondrial y reducir la capacidad del tejido muscular para generar energía eficientemente. Este estrés oxidativo exacerbado durante el ejercicio puede llevar a daño celular y fatiga muscular.

𝐀𝐥𝐭𝐞𝐫𝐚𝐜𝐢𝐨𝐧𝐞𝐬 𝐞𝐧 𝐥𝐚 𝐟𝐮𝐧𝐜𝐢𝐨́𝐧 𝐫𝐞𝐬𝐩𝐢𝐫𝐚𝐭𝐨𝐫𝐢𝐚: La función respiratoria puede verse afectada, limitando la oxigenación adecuada durante el ejercicio y contribuyendo a la fatiga.

𝐈𝐧𝐟𝐥𝐚𝐦𝐚𝐜𝐢𝐨́𝐧 𝐬𝐢𝐬𝐭𝐞́𝐦𝐢𝐜𝐚: La activación de ciertos receptores, la liberación de citocinas proinflamatorias y otros mecanismos asociados con la infección crónica pueden generar una inflamación sistémica. Esta inflamación puede afectar negativamente la capacidad del cuerpo para recuperarse después del ejercicio, contribuyendo al malestar-postesfuerzo.

𝐀𝐥𝐭𝐞𝐫𝐚𝐜𝐢𝐨𝐧𝐞𝐬 𝐞𝐧 𝐥𝐚 𝐟𝐮𝐧𝐜𝐢𝐨́𝐧 𝐧𝐞𝐮𝐫𝐨𝐥𝐨́𝐠𝐢𝐜𝐚: Los cambios metabólicos y la inflamación sistémica pueden tener un impacto en el sistema nervioso central. La reducción en la disponibilidad de serotonina y otras alteraciones pueden contribuir a la sensación de fatiga y letargo.

¿𝐄𝐬𝐭𝐞 𝐦𝐨𝐝𝐞𝐥𝐨 𝐞𝐱𝐩𝐥𝐢𝐜𝐚 𝐥𝐚 𝐝𝐢𝐬𝐚𝐮𝐭𝐨𝐧𝐨𝐦𝐢́𝐚 𝐩𝐫𝐞𝐬𝐞𝐧𝐭𝐞 𝐞𝐧 𝐞𝐬𝐭𝐨𝐬 𝐩𝐚𝐜𝐢𝐞𝐧𝐭𝐞𝐬?
Si, a continuación, desgloso cómo el modelo puede generar disautonomía:

- 𝐈𝐧𝐟𝐞𝐜𝐜𝐢𝐨́𝐧 𝐩𝐨𝐫 𝐄𝐁𝐕: La incapacidad para controlar adecuadamente las células de latencia I del EBV podría resultar en respuestas inflamatorias crónicas, lo que perturba la homeostasis del sistema inmunológico y, por extensión, afecta al sistema nervioso autónomo (SNA).

-𝐑𝐞𝐬𝐩𝐮𝐞𝐬𝐭𝐚𝐬 𝐢𝐧𝐟𝐥𝐚𝐦𝐚𝐭𝐨𝐫𝐢𝐚𝐬: Las citocinas proinflamatorias liberadas en respuesta al EBV, como IL-1β, IL-6 y TNF-α, pueden actuar en el cerebro y otros órganos, alterando la función del SNA, lo que lleva a síntomas de disautonomía.

-𝐀𝐥𝐭𝐞𝐫𝐚𝐜𝐢𝐨𝐧𝐞𝐬 𝐦𝐞𝐭𝐚𝐛𝐨́𝐥𝐢𝐜𝐚𝐬: La hipozincemia y las alteraciones en el transporte de cobre pueden desequilibrar la función de enzimas claves, como la DAO. Una función deficiente de la DAO lleva a una acumulación de histamina, un mediador que puede causar síntomas de disautonomía, como vasodilatación y arritmias.

- 𝐀𝐥𝐭𝐞𝐫𝐚𝐜𝐢𝐨𝐧𝐞𝐬 𝐠𝐚𝐬𝐭𝐫𝐨𝐢𝐧𝐭𝐞𝐬𝐭𝐢𝐧𝐚𝐥𝐞𝐬: La acumulación de serotonina en el intestino puede estimular al nervio vago, una conexión primordial entre el intestino y el cerebro. La sobreestimulación del nervio vago puede desencadenar síntomas de disautonomía, como bradicardia.

-𝐀𝐥𝐭𝐞𝐫𝐚𝐜𝐢𝐨𝐧𝐞𝐬 𝐧𝐞𝐮𝐫𝐨𝐥𝐨́𝐠𝐢𝐜𝐚𝐬: Una disminución en la serotonina extracelular cerebral y un aumento en metabolitos neurotóxicos del kynurenina pueden alterar la función neuronal y del SNA, lo que podría manifestarse como fatiga, intolerancia al ejercicio y otros síntomas de disautonomía.

- 𝐀𝐥𝐭𝐞𝐫𝐚𝐜𝐢𝐨𝐧𝐞𝐬 𝐯𝐚𝐬𝐜𝐮𝐥𝐚𝐫𝐞𝐬: La formación de microcoágulos puede afectar la perfusión sanguínea adecuada en órganos y tejidos, incluyendo el cerebro. Una perfusión inadecuada puede resultar en síntomas neurológicos y autonómicos.

-𝐀𝐥𝐭𝐞𝐫𝐚𝐜𝐢𝐨𝐧𝐞𝐬 𝐞𝐧𝐝𝐨𝐜𝐫𝐢𝐧𝐚𝐬: La hiperinsulinemia y la posible reducción en la secreción de cortisol pueden afectar el equilibrio del SNA. Por ejemplo, la hipoglucemia puede desencadenar una respuesta simpática aguda, mientras que la disminución del cortisol puede afectar la capacidad del cuerpo para manejar el estrés.

¿𝐄𝐬𝐭𝐞 𝐦𝐨𝐝𝐞𝐥𝐨 𝐞𝐱𝐩𝐥𝐢𝐜𝐚 𝐥𝐚 𝐧𝐞𝐮𝐫𝐨𝐢𝐧𝐟𝐥𝐚𝐦𝐚𝐜𝐢𝐨́𝐧, 𝐥𝐚 𝐧𝐢𝐞𝐛𝐥𝐚 𝐦𝐞𝐧𝐭𝐚𝐥 𝐲 𝐞𝐥 𝐝𝐞𝐭𝐞𝐫𝐢𝐨𝐫𝐨 𝐜𝐨𝐠𝐧𝐢𝐭𝐢𝐯𝐨?
Sí, este modelo presentado podría explicar la neuroinflamación, la niebla mental y el deterioro cognitivo de la siguiente manera:

1️⃣𝐍𝐞𝐮𝐫𝐨𝐢𝐧𝐟𝐥𝐚𝐦𝐚𝐜𝐢𝐨́𝐧: En pacientes con ME/CFS y LC, hay evidencia de infección viral crónica o reactivación de virus, especialmente EBV. Cuando hay presencia de material genético viral, especialmente EBERs del EBV, se activan los receptores TLR3 en la microglía (células inmunológicas del sistema nervioso central). Esta activación resulta en la liberación de citocinas proinflamatorias como IL-1β y TNF-α. Estas citocinas pueden contribuir a la inflamación crónica del sistema nervioso central, caracterizando la neuroinflamación.

2️⃣𝐍𝐢𝐞𝐛𝐥𝐚 𝐦𝐞𝐧𝐭𝐚𝐥 𝐲 𝐝𝐞𝐭𝐞𝐫𝐢𝐨𝐫𝐨 𝐜𝐨𝐠𝐧𝐢𝐭𝐢𝐯𝐨: Varias vías mencionadas en el modelo pueden contribuir a estos síntomas. Por ejemplo:
-La infección viral puede causar daño a la barrera hematoencefálica, permitiendo la entrada de material genético viral que podría activar aún más la microglía y contribuir a la neuroinflamación.

-El aumento de la actividad de IDO y la disminución de los niveles de triptófano llevan a una reducción en la síntesis de serotonina (5-HT) y melatonina. Dado que la serotonina juega un papel en la regulación del estado de ánimo, la cognición y la alerta, su reducción podría contribuir a la niebla mental.

-El ácido quinolínico, un metabolito del triptófano, tiene propiedades neurotóxicas al unirse al receptor NMDA, lo que puede aumentar el estrés nitrosativo y contribuir al deterioro cognitivo.

-El aumento del estrés oxidativo y nitrosativo en células infectadas por EBV, junto con la neuroinflamación, puede interferir con el correcto funcionamiento neuronal y contribuir al deterioro cognitivo.

-Las alteraciones en el sistema serotonérgico también pueden afectar directamente la función cognitiva y la percepción de fatiga.

𝐂𝐨𝐧𝐭𝐢𝐧𝐮́𝐚 𝐞𝐥 🧵👇🏽

𝐋𝐢𝐧𝐤 𝐄𝐬𝐭𝐮𝐝𝐢𝐨:

#VirusEpsteinBarr #EBV #LongCovid #EMsfc #EncefalomielitisMialgica #Salud #investigacion #Noticias #microE2324 #Medicina #Virus #Microbiología #EnfermedadesCronicas
@drmiguelmarcos @DoctorCasado @MasTwitts
Este modelo explica la aparición de problemas digestivos, intolerancias alimentarias y alteraciones en la microbiota en estos pacientes?

Sí. A continuación, te resumo los puntos clave:
1️⃣Problemas digestivos:
-La acumulación de 5-HT (serotonina) en la mucosa intestinal provoca inflamación crónica.
-Esta inflamación intestinal lleva a una disminución en la secreción ácida del estómago y en la expresión de enzimas necesarias para digerir carbohidratos. Como resultado, más carbohidratos llegan a la microbiota intestinal sin ser digeridos o absorbidos, lo que puede causar problemas digestivos como distensión, gas y diarrea.
La alteración serotonérgica, junto con el aumento de citocinas proinflamatorias, provoca una alteración en la secreción ácida, descomposición de la barrera intestinal y disminución en la expresión de enzimas necesarias para digerir carbohidratos.

🔬 𝐄𝐱𝐜𝐢𝐭𝐢𝐧𝐠 𝐮𝐩𝐝𝐚𝐭𝐞! Findings from the @VirusesImmunity study support our review article on the relationship between EBV and symptoms in #LongCovid and #MECFS . I've detailed this connection below. 🧬 #ResearchUpdate #EBVLink.

https://twitter.com/VirusesImmunity/status/1706332965792272722

1/ Many wonder why EBV is the main trigger for ME/CFS and Long COVID symptoms, over other factors such as other infections and metal poisoning. Let's dive into it, summarizing our recent review article. Link: link.springer.com/article/10.118…

🔥🧬 NEW PAPER PUBLISHED! Is there a link between EBV (Epstein-Barr Virus) and conditions such as myalgic encephalomyelitis and Long COVID? 🤔🌍 Dive into this thread and discover how EBV could be behind the symptoms of both pathologies and what therapeutic strategies exist: ⬇️🔍 1/ 🤔 𝐈𝐧𝐭𝐫𝐨𝐝𝐮𝐜𝐭𝐢𝐨𝐧: ME/CFS and Long COVID are two pathologies that, although arising from different causes, present astonishing similarities in how they affect the body and their symptoms. #MyalgicEncephalomyelitis #COVIDSurvivors

Paper link: link.springer.com/article/10.118…

Thread 🧵👇:
After so many years of work and as a post Epstein-Barr virus infection #MECFS sufferer it makes me really happy that they have put our article on the cover of the August issue of Pathogens journal 👉:mdpi.com/2076-0817/11/8
(1/) Until recently nobody talked about post-viral syndromes (actually they should be called chronic infectious syndromes) and they left all of us patients isolated both at a health and social level. Unfortunately it took another virus like #SARSCoV2 to show us how viruses are ...(2/)

A long thread 👇🏼:
I would like to share with you my latest review article. The Epstein-Barr virus (EBV) has long been known to be behind the development of autoimmune diseases, cancer and is even suspected to be behind the development of Chronic Fatigue Syndrome/… (1) …Myalgic Encephalomyelitis and Long COVID. But it is still unclear what pathways it uses.

In this review I describe how the possession of certain ancestral HLA-II alleles (a system used by our immune system to recognize which proteins are foreign,… (2)

Te respondo con otro hilo 😅

La cuantificación del virus de Epstein-Barr utilizando la técnica PCR en sangre normalmente sale negativo en estos pacientes, puesto que el problema son las células con latencia del virus. (1)

https://twitter.com/lightup_thepath/status/1551642499604692994

Hay que realizar la prueba en lugares donde haya acumulación de estas células, es decir, en tejido, por ejemplo, en la mucosa intestinal. (2)

Abro hilo largo👇
Me gustaría compartir con vosotros mi último artículo de revisión. Desde hace mucho tiempo se sabe que el virus de Epstein-Barr (EBV) está detrás del desarrollo enfermedades autoinmunes, cáncer e incluso se sospecha que está detrás... (1) ...del desarrollo de Síndrome de Fatiga Crónica/Encefalomielitis Miálgica y del Long COVID. Pero todavía no está claro las vías que utiliza. En esta revisión describo como la posesión de ciertos alelos ancestrales de HLA-II... (2)