Rheumatoid Arthritis, Molecular Mimicry, and Diet as a Possible Therapy
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

"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. 
For further information on ELISA testing:

1. Tortora & Grabowski _Principles of Anatomy and Physiology_ 1996
HarperCollins, N.Y. p. 234

2. Tiwana H, et al.  Cross-reactivity between the rheumatoid
arthritis-associated motif EQKRAA and structurally related sequences found
in proteus mirabilis. Infect Immun. 1999 Jun;67(6):2769-75. 

3. Husby S, et al. Passage of undegraded dietary antigen into the blood of
healthy adults. Quantification, estimation of size distribution, and
relation of uptake to levels of specific antibodies. Scand J Immunol. 1985

4. Reunala T, et al. Diseases associated with dermatitis herpetiformis. Br
J Dermatol. 1997 Mar;136(3):315-8. 

5. Lepore L, et al. Prevalence of celiac disease in patients with juvenile
chronic arthritis.  J Pediatr. 1996 Aug;129(2):311-3

6. Paimela L, et al.  Gliadin immune reactivity in patients with rheumatoid
arthritis. Clin Exp Rheumatol. 1995 Sep-Oct;13(5):603-7. 

7.Lepore L, et al.  Anti-alpha-gliadin antibodies are not predictive of
celiac disease in juvenile chronic arthritis. Acta Paediatr. 1993

8.  Carli P, et al. [Inflammatory rheumatism and celiac disease in adults.
Coincidence or pathogenic relationship]? Presse Med. 1995 Apr
1;24(13):606-10. French. 

9. Collin P, et al.  Rheumatic complaints as a presenting symptom in
patients with coeliac disease. Scand J Rheumatol. 1992;21(1):20-3. 

10. Koot VC, Van Straaten M, Hekkens WT, Collee G, Dijkmans BA,  "Elevated
level of IgA gliadin antibodies in patients with rheumatoid arthritis"
_Clin Exp Rheumatol_ 1989 Nov;7(6):623-626