You are leaving Medscape Education
Cancel Continue
Log in to save activities Your saved activities will show here so that you can easily access them whenever you're ready. Log in here CME & Education Log in to keep track of your credits.


Selective Costimulation Modulators: Addressing Unmet Needs in Rheumatoid Arthritis Management: Genetics and RA


Genetics and RA

As suggested by RA concordance in twins in the previously described studies, the likelihood of developing RA is influenced to a significant degree by genetic factors. Polymorphisms of several genes that are important in the regulation of immune responses have been linked to an increased risk of developing RA. Many high-risk alleles have been identified in MHC class II genes, including HLA-DQB1, HLA-DQA1, and especially HLA-DRB1.[10] The HLA-DR4 region of the HLA-DRB1 gene cluster is strongly associated with an increased risk of severe and persistent RA.[10] The risk of RA associated with all of the high-risk HLA-DR4 alleles has been attributed to the presence of 1 of 3 specific amino acid sequences, comprising amino acids 70-74. These shared epitopes consist of various sequences of the amino acids glutamine (Q), leucine (K), arginine (R), and alanine (A): QKRAA, QRRAA, or RRRAA.[11] In monozygotic twins, the homozygous presence of either the QKRAA or QRRAA epitope in HLA-DR4 confers a 5-fold increase in the risk of developing RA.[12] Thus, it has been hypothesized that RA may be initiated when RA-associated MHC molecules present self-antigens to autoreactive T cells, although the antigens involved in this process have not been definitively identified.[10]