The discovery of a cause, as well as treatment, for Rheumatoid Arthritis (RA) may involve our commensal gut bacteria.
Millions of adults suffering from RA experience chronic pain, chronic inflammation, and often severe functional disability of the joints. Onset in older populations is a well-known risk factor, and RA is three times as likely in women.(1)
Many anecdotes of restrictive diets alleviating the severity of arthritic symptoms inspired scientific inquiry. A 13-month long study evaluating clinical variables such as pain, swelling, and grip strength after switching to a plant-based diet was performed on RA patients. The controlled, single-blind trial demonstrated some patients placed on a plant-based diet had positive effects on clinical variables.(2)
A particularly interesting factor is the genetic component of RA. The disease occurs predominantly in individuals expressing HLA-DR1 or HLA-DR4, proteins related to immune function. The human leukocyte antigen (HLA) system or complex is a composite of genes on chromosome 6 in humans which encode cell-surface proteins responsible for the regulation of the immune system. These proteins found on the surface of the HLA system are also known as the human version of the major histocompatibility complex (MHC) found in many animals. These HLA proteins are found on the surface of dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells, and are instrumental in initiating an immune response. Researchers discovered a common amino acid sequence found in both HLA-DR1/4, thus named the “shared epitope.”
Investigations into the ‘shared epitope’ demonstrated potential cross-reactivity with Proteus hemolysin. Serological studies showed rabbits injected with Human HLA-DR4 lymphocytes produced sera with specificity against Proteus mirabilis and Proteus vulgaris.(3) Another sequence from type XI collagen found in joints was shown to resemble the urease enzyme produced by Proteus. In the diagram above you can see the similarity in protein structure between joint collagen and Proteus urease, which presumably confuses the immune system.
The evidence paints RA as a case of molecular mimicry; Proteus inducing an autoimmune response in at-risk individuals.
Bacterial molecular mimicry is not uncommon. It is infamous for its role in rheumatic fever, where anti-Streptococcal antibodies target antigens in the heart.(4) It is likely that the immune response to Proteus, particularly in HLA-DR1/4-positive individuals, is behaving in a similar way. This answer can also explain the female susceptibility to RA, as women are more likely to acquire Proteus mirabilis-related UTIs than men.
One question remains: How could diet alleviate arthritic symptoms?
In the plant-based diet study, antibody activity measured in the RA patients showed a significant drop in anti-Proteus mirabilis IgG for those who switched to the plant-based diet. The decline was more noticeable in patients who responded to the diet, and it was present just a few months after the plant-based diet began. From this we can infer that the plant-based diet quickly lowers the population of Proteus in the gut of RA patients, therefore reducing the autoimmune attack.
Take some time to evaluate your diet; the wrong one could take a toll on your health!
By Manuel Escalera
Performance Studies Technician