My thoughts on late manifestations of Lyme disease (Stage 3 "Chronic Lyme") & major histocompatibility complex (MHC)
Expression of MHC decrease in Langerhans' cells in the skin of patients with acrodermatitis chronica atrophicans #LymeDisease onlinelibrary.wiley.com/doi/abs/10.104…
Despite a strong immune response against B. burgdorferi the infection can become chronic, even after several courses of antibiotic treatment. #Lyme arthritis is one of those manifestations.
The cause chronic Lyme disease remains a topic debate between persistent infection and/or autoimmunity.

For example: Autoantigen in Treatment-Resistant Lyme Arthritis science.sciencemag.org/content/281/53…
and

Autoimmune Mechanisms in Antibiotic Treatment-Resistant Lyme Arthritis sciencedirect.com/science/articl…
There is evidence that T-lymphocytes (which activate macrophages) play a role in chronic Lyme arthritis.

In this study "Macrophages exposed to Borrelia burgdorferi induce Lyme arthritis in hamsters." iai.asm.org/content/64/7/2…
and

Macrophages and enriched populations of T lymphocytes interact synergistically for the induction of severe, destructive Lyme arthritis. iai.asm.org/content/65/7/2…
The macrophages result in increased levels of interleukin-1, & tumour necrosis factor--both are proinflammatory cytokines.
For example: "Isolation of interleukin 1 from joint fluids of patients with Lyme disease." europepmc.org/article/med/27…
and

"In vitro and in vivo induction of tumor necrosis factor alpha by Borrelia burgdorferi." iai.asm.org/content/60/3/1…
IL-1 + TNF activate osteoclastic cartilage and bone reabsorption and may play a BIG role in Lyme arthritis.

"Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors." nature.com/articles/31951…
macrophages can stimulate nitric oxide which is associated with other forms of arthritis.

"Outer surface lipoproteins of Borrelia burgdorferi stimulate nitric oxide production by the cytokine-inducible pathway." iai.asm.org/content/62/9/3…
One potential explanation for antibiotic resistant Lyme arthritis is molecular mimicry. sciencedirect.com/topics/medicin…
There has also been an "Association of Chronic Lyme Arthritis with HLA-DR4 and HLA-DR2 Alleles" suggesting a genetic link to the disease. nejm.org/doi/full/10.10…
👆These patients appear to have an autoimmune-type response to B.b. OspA.

"Early and late antibody responses to full-length and truncated constructs of outer surface protein A of Borrelia burgdorferi in Lyme disease." iai.asm.org/content/63/6/2…
Where the T-cells contribute to the "Pathogenesis of Treatment-Resistant Lyme Arthritis" link.springer.com/article/10.100…
This study shows the way in which dendritic cells and MHC may influence the immune response in Lyme disease.

Human dendritic cells phagocytose and process Borrelia burgdorferi. jimmunol.org/content/157/7/…
This figure summarises these findings schematically, and suggests the possibility that intracellular persistence of B. burgdorferi in synovial cells might contribute to this scenario of #Lyme arthritis. /end sciencedirect.com/science/articl… Image
And yes. Mast cells are found in the synovium and synovial fluid in osteoarthritis. ncbi.nlm.nih.gov/pubmed/8348268

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More from @LonnieRhea

12 Jul
New | Lyme arthritis: linking infection, inflammation and autoimmunity. #LymeDisease (a thread) 1/
nature.com/articles/s4158…
"In the USA, B. burgdorferi often disseminates in the blood during the first few weeks of infection in a process that requires the binding of Borrelia surface adhesins to host integrins on the vascular endothelium28–30. " 2/ Image
"As shown in mice, the spread of B. burgdorferi through the vasculature or lymphatics is dependent on the inter-actions of spirochaetal surface molecules and endothe-lial cell membrane proteins." 3/
Read 29 tweets
3 Feb
Thread: A major barrier to progress in understanding the neurologic manifestations of #LymeDisease has been a lack of a tractable laboratory animal model to evaluate the mechanisms of central nervous system pathogenesis.
For decades we have seen study after study of Lyme arthritis. As it turns out the most frequently reported Lyme symptoms are neurological symptoms: memory loss and cognitive impairment, sleep impairment, psychiatric manifestations, headaches, neuropathy and more. 2/
This is the first study, to my knowledge, that shows how Borrelia burgdorferi gets into the central nervous system, how the immune system responds, and how the bacteria adapt to the immune system. #Lyme
Meet the researcher Catherine Brissette, Ph.D. globallymealliance.org/meet-researche…
Read 15 tweets
23 Sep 20
In an encouraging development yesterday @CDC_NCEZID representative Ben Beard made an important announcement--a new "national strategy" for vector-borne diseases. I'll explain in a thread 1/n
lymedisease.org/framework-vect… via @Lymenews
The Kay Hagan Tick Act, passed in 2019, called for @hhs to develop a national strategy to address issues related to vector-borne diseases. The Lyme community fought hard for the passage of the #TICKact lymedisease.org/tick-act-appro… via @Lymenews 2/
The idea was for @HHSGov to co-ordinate with other federal agencies and departments, including the @CDCgov @EPA @US_FDA @NIH @DeptofDefense @USDA @USGS and others, to get everybody working towards the same goals. 3/ Image
Read 12 tweets
9 Aug 20
The geothermal features in Yellowstone are amongst my top 10 favorite sites on this planet. Here’s a bit of #microbio history on the PCR test I’d like to share.
Pictured: Grand Prismatic at the Midway Geyser Basin @YellowstoneNPS
“Until the 1980s, our ability to study DNA was limited. Things we take for granted today such as DNA fingerprinting to identify criminals, DNA medical diagnoses, DNA-based studies of nature, and genetic engineering did not exist.”
“But in 1985, the polymerase chain reaction (PCR) was invented. PCR is an artificial way to do something that living things do every day—replicate DNA. PCR is the rocket ship of replication, because it allows scientists to make billions of copies of a piece of DNA in a few hours.
Read 7 tweets
26 Jun 20
What has the #Lyme community learned from the #COVID19 pandemic?
thread...
lymedisease.org/bureaucratic-d…
(1) In a matter of weeks, the federal government can allot trillions of dollars to one disease.
2) In a matter of weeks, the @CDCgov can develop and mass produce a new test.
Read 6 tweets
3 Apr 20
Thread. @Sermo survey of 6,227 physicians worldwide: 85% of US physicians report #COVID19 testing takes 2-5 days or longer, while nearly half of international physicians report testing is completed within just 24 hours. Image
Survey @Sermo says, 91% of US physicians and 83% of international physicians say the status of #COVID19 testing is far below what is needed. Image
Survey @Sermo says "Physicians most request life science firms develop new rapid tests for COVID-19, followed by new drugs that offer immunity to front-line workers and accelerate efforts to test existing drugs to treat #COVID19" Image
Read 4 tweets

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