Hypothesized Causes of Rheumatoid Arthritis

The causes of rheumatoid arthritis (RA) and most autoimmune diseases are unknown.[1] These related autoimmune diseases include celiac, type 1 diabetes, lupus, multiple sclerosis, and ulcerative colitis among others and they impact millions of people. That’s a sad thing since these diseases are insidious. Because of the lack of definitive information about the underlying causes of these diseases, there are many speculations running wild around the internet and unsuspecting sufferers look for answers from any place they can find it often leading to various home remedies.

Since being diagnosed with rheumatoid arthritis, my curiosity and scientific background pushed me deep into the research literature in order ferret out a cause for RA. While the research literature is somewhat sparse in this field, by far the most comprehensive work is from Dr. Alessio Fasano from the University of Maryland School of Medicine. He has an excellent article called “Surprises from Celiac Disease” published in the August 2009 issue of Scientific American.[2] While most of Fasano’s research is with celiac disease, a problem digesting the gluten protein in wheat, his work is beginning to shed light on the causes of other autoimmune diseases. He notes that a trio of triggers seems to be present and include 1. an environmental trigger, 2. a genetic susceptibility, and 3. a “leaky gut”.

With rheumatoid arthritis, scientists have long suspected that an infection of some sort, an environmental trigger, sets off the immune system to begin to attack the body's own tissues. That’s why some of the early medicines, like sulphasalazine, were derived from antibiotics. Some still advocate long term antibiotic therapy for RA such as the Roadback Foundation which is devoted to advocating for antibiotic protocol for RA.[3] But infectious triggers have never been completely pinpointed nor fully used to explain the cause of the disease leading to widespread treatments.

Genetics also seem to be connected. Many people suffering from autoimmune diseases show a genetic marker for some type of histocompatibility leukocyte antigen (HLA).[4] HLA proteins bind to objects that they mistakenly recognize as foreign in the body.  This sets off an immune response where T lymphocytes recognize the object as “foreign”, call in reinforcements, and the immune system then fights the supposed “invaders” resulting in the body attacking it's own tissue. During this process powerful inflammatory chemicals called cytokines are released. These cause the symptoms of RA and other autoimmune diseases. Cytokine receptors, like tumor necrosis factor (TNF), have been the target of RA research for the past 20 years and resulted in powerful RA drugs like Enbrel and Humira. A detailed description of these processes can be found at Johns Hopkin’s rheumatology website.[5] Some researchers propose that genetic switches may get turned on from certain environmental factors which then  trigger autoimmune processes to be initiated.[6]

But neither infection nor genetics fully explains a cause for rheumatoid arthritis. This leads to the third factor in the proposed trio of triggers – the so called “leaky gut”. This somewhat controversial trigger has been getting airplay in the internet for some time.[7] The prominent and highly interactive relationship between the immune system and the intestines is becoming clearer.[8] That makes sense because we ingest so many things into our bodies through our mouths. Our defense system must be ready to combat invaders. The intestines normally have a tight wall that keeps particles from leaking into the rest of the body. Dr. Fasano’s work with celiac patients is shedding light on how increased permeability of the intestines allows proteins to leak out into the body where they are immediately attacked by the immune system. The role of this in autoimmune diseases is speculative at this point and there is not a wide body of scientific research to completely support it. But some relief has been found in some people by controlling their diet - milk and wheat proteins being the most common. A variety of dietary changes may have an impact on inflammatory symptoms [ix] but there is not a generalized recommendation that all RA patients go gluten or lactose free as a treatment. Much more research needs to occur in order to determine what role, if any, the digestive/immune system connection plays in the processes of the disease.

There are many more questions than answers right now and the definitive causes of RA remains unknown. But there is work in this area and a quote from the Scientific American editors about Fasano’s article sums it up, “Surprisingly, essentially the same trio …seems to underlie other autoimmune disorders as well. This finding raises the possibility that new treatments for CD (celiacs) may also ameliorate other conditions.” This gives hope. Perhaps not for current patients directly since new and complicated medicines take many years to develop, test, and market. But there is hope for the millions of future sufferers of autoimmune disorders. The goal of such research into the causes of RA could potentially lead to better treatments and ultimately, a cure.

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This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The RheumatoidArthritis.net team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

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