Rheumatoid Arthritis, Molecular Mimicry, and Diet as a Possible Therapy
by Ron Hoggan
Rheumatoid arthritis (RA) is an autoimmune disease where the body attacks its own cartilage and joint linings. It is characterized by swelling and pain. The synovial membrane at afflicted joints goes through several abnormal stages of autoimmune damage, ultimately destroying the cartilage and fusing the bones with fibrous tissues that may ossify, eliminating joint mobility (1).
This is all very interesting, but it fails to capture the real nature of RA. It is darned painful, and can be very frustrating. Every practitioner seems to have a different answer that either doesn't work, or has so many side effects that it is only marginally worthwhile to take the prescribed medications. And it sometimes seems that there is a new answer every week.
But there is a new paradigm in autoimmunity. It offers a profoundly more hopeful perspective than has been possible in the past. If the notion of molecular mimicry is substantiated in RA, which seems likely, given the recent exponential increase in researchers' interest in this area. By my count, more than 80% of the research connecting RA with molecular mimicry, as reported on Medline, has been reported during the last decade.
Some researchers are looking for a protein, or partial protein (peptide), from a chronic infectious agent that might reside in the gut, and regularly be transported across a permeable intestinal wall into the circulation. Others are searching for a specific bacterium or virus that has an amino acid sequence that would serve as a trigger for production of antibodies against that "invader". The assumption is, of course, that the antibodies in question would attack tissues with similar sequences of amino acids in their protein structures. The immune system would start out mounting an attack against a foreign substance, and wind up attacking the collagenous tissues at the joints, as in RA.
There is considerable interest in this area, and I believe it warrants exploration. However, I am disposed to the application of the theory of molecular mimicry, to RA, in a little different manner. Infectious agents often come and go. Yet autoimmune diseases usually progress, either steadilly, or through cycles of remission and relapse. This may be an important flaw in the application of the theory of molecular mimicry to infectious agents.
What foreign proteins find their way into the blood on a continuous basis? There is clear evidence that some of the alcohol soluble proteins from farinacious grains are regularly absorbed into the blood (3). Since these grains serve as a daily staple in the diets of virtually everyone living in the industrial world, such grains are a likely prospect for initiating and perpetuating a dynamic of molecular mimicry leading to rheumatoid arthritis.
On the strength of this evidence alone, a gluten-free diet should be given an empirical trial with every RA patient, but there is much more evidence suggesting the need for such a trial. It has been reported that celiac disease, a disease characterized by an intestinal inflammatory response to farinacious grains, is associated with endocrine or connective tissue disorders (4) and that celiac disease is overrepresented in connective tissue disease, including RA (5). This lends further implicit support to the notion that gluten-containing grains may be a factor in at least some cases of RA. In fact, one group reported that 37% of their RA patients demonstrated elevated antibodies against gliadin (6). Although it is important to note that the presence of these antibodies are often not predictive of celiac disease the following conclusion warrants careful reading:
"CONCLUSION. Despite the increased AGA positivity found distinctively in patients with recent-onset RA, none of the RA patients showed clear evidence of coeliac disease. AGA positivity in early RA may indicate a role of the gut immune system in the initiation of RA." (6)
Perhaps the most compelling evidence for a causal relationship between gluten and some cases of RA may be found in the reports that in patients where both celiac disease and RA are diagnosed, the gluten free diet is often an effective treatment for both conditions (8,9)
Not surprisingly, this new understanding serves as something of an indictment of some current practices in the treatment of RA. Koot et al. conclude their report with the following statement: "The elevated IgA antigliadin titre in the RA group might be ascribed to the use of NSAIDs, which are harmful to the gut, but the immunological trigger effect of gluten cannot be ruled out"(10). It is important to manage pain, but it is also important to limit any self-perpetuating impact of analgesics.
The theory of molecular mimicry offers new hope to those who suffer from RA, and there is a compelling alternative to waiting for the current search to exhaust the field of infectious agents, and begin to investigate dietary antigens as a possible trigger and perpetuating factor in RA. ELISA testing offers to identify specific dietary antigens that may be at work in RA. In a large number of cases this will likely include gluten, but may not be restricted to gluten alone. Milk protein is also relatively new to the human diet, and may also need to be excluded. Caseins, proteins found in dairy products, are structurally similar to gluten, and are also likely candidates for inciting autoimmune dynamics through the dynamic of molecular mimicry. In other cases, perhaps additional dietary antigens will also need to be removed from the diet.
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