Thread by @LonnieRhea

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…

And yes. Mast cells are found in the synovium and synovial fluid in osteoarthritis. ncbi.nlm.nih.gov/pubmed/8348268