Chromosomes
My curiosity about genetics and RA was peaked again today when I saw a post on the Facebook page of the American Autoimmune Related Diseases Association (AARDA). A publication from 2004 suggested a possible genetic link between an immune response to tuberculosis over the past few hundred years and autoimmune diseases including rheumatoid arthritis.[i] The notion is that survival of bacteria-induced tuberculosis resulted in the genetic selection of proteins connected with RA including TNF-alpha and HLA. In other words, people that survived tuberculosis had the genes to produce more of these proteins. And people whose genes resulted in the production of certain proteins resulted in more cases of RA. While the exact causes of RA are complex and not entirely known, this study lends more evidence to the notion that there is an underlying genetic connection. Some evidence also exists for environmental and even bacterial triggers for RA (see my earlier posts). Most scientists believe that RA is caused by both genetic and environmental triggers.
For anyone on Humira, Enbrel, or Remicade, TNF-alpha should be familiar since those biological medicines work to block TNF-alpha in the biochemical processes. TNF alpha is a cytokine (protein) that causes inflammation. People with RA and other autoimmune diseases show an overproduction of TNF-alpha. Thus, blocking TNF became a recent mainstay in the treatment of RA.
The human leukocyte antigens (HLA) are a group of genes on chromosome 6 that are connected with the immune system.[ii] There are many autoimmune diseases connected with HLA genes and a scientist in the UK maintains a website is devoted to the topic – http://www.hladiseaseassociations.com/. Multiple HLA genes are connected with rheumatoid arthritis including HLA-DR4 and HLA-DRB. While HLA genes are commonly connected with RA, some scientists demonstrated that other genes also play a role.[iii] One gene called, HLA-B27, is associated with ankylosing spondylitis (AS), an autoimmune disease that impacts the spine, hips, and ankles. I tested negative for this gene several years ago although my rheumatologist noted that some of my symptoms resemble AS. But not all people with AS have the gene and not all people with the gene have AS.
My rheumatologist really grabbed my attention recently when she suggested that I participate in a genetic study since I display symptoms of multiple autoimmune diseases along with mixed genetic and blood tests (rheumatoid factor positive, HLA-B27 negative). Consumer-based companies will conduct basic genetic testing for a cost (e.g. https://www.23andme.com). Kelly at RA Warrior wrote an informative blog about consumer testing last year. I would prefer to engage in a scientific study and I plan to raise this topic at my next doctor appointment. Stay tuned for test results!
