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The Role of the Laboratory in the Diagnosis of Rheumatoid Arthritis



Risk Factors Associated with Development of Rheumatoid Arthritis

Slide 3

August 2011

As I just stated, there are multiple risk factors, both environmental and genetic, that may predispose an individual to developing rheumatoid arthritis.

There is a gender bias in rheumatoid arthritis, as is seen in many autoimmune diseases. Rheumatoid arthritis is 2 to 3 times more common in females than in males. Although this is thought to be related to hormonal differences, the specific cause of this bias is not known.

Cigarette smoking is another important risk factor. Although the reason for this is not well understood, recent studies have shown that cigarette smoke is associated with increased protein citrullination and may lead to the development of anti-CCP antibodies, which we will discuss shortly.

Lastly, as far as environmental factors go, infection may also play a role in the pathogenesis of rheumatoid arthritis. Although no specific bacteria or virus has been identified as a causative agent, it is hypothesized that infection, in certain individuals, may alter the immune response, resulting in a chronic autoimmune process.

With regard to the genetic component, individuals with a history of autoimmune disease in their family, or individuals with a first-degree relative with rheumatoid arthritis, are more at risk for developing the disease. Rheumatoid arthritis is a multigenic disease, meaning that the effect of many genes combine to predispose an individual to developing the disease.

Much of the genetic susceptibility has been linked to the MHC class II genes. The research that has gone on in this field has led to the shared epitope hypothesis. The MHC genes that are associated with rheumatoid arthritis, specifically certain HLA-DR4, HLA-DR1, and HLA-DR6 alleles, all share a similar amino acid sequence, referred to as the “shared epitope”, within the HLA-DR beta chain. Again, how this is related to the pathogenesis of rheumatoid arthritis is not known. However, it is thought that perhaps this sequence may be responsible for presenting a specific autoantigen that initiates or prolongs the immune response, or that perhaps these alleles result in preferential selection of autoreactive lymphocytes during development.

Another genetic risk factor that has been discovered is PTPN22. This gene encodes for a protein tyrosine phosphatase that is partially responsible for regulating T-cell activation. A specific polymorphism, which is designated as R620W, has been shown to be found more frequently in individuals with autoimmune disease, including rheumatoid arthritis, than in healthy individuals. Data also suggest that heterozygosity or homozygosity for this polymorphism predisposes patients with rheumatoid arthritis to having a more aggressive disease course.

Risk Factors Associated with Development of RA

 


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