Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Rheumatoid Arthritis (HLA-DRB1 Typing) [M05, M06]

OMIM number: 180300, HLA-DRB1 (142857), 147781 (IL4R)

Dr. med. Kaimo Hirv

Scientific Background

With a prevalence of approximately 1%, rheumatoid arthritis (RA) is the most frequently occurring autoimmune disease among the Western European population. Until today, the cause of the disease has only been partially understood. There is no doubt that genetic factors play an important role. Especially certain HLA-DRB1*04 alleles (DR4), but also other HLA alleles such as HLA-DRB1*01:01, *01:02, *10:01 and *14:02 have been associated with RA. These HLA alleles encode an amino acid motif, also referred to as “shared epitope (SE) or “rheumatoid epitope”. Approximately 80-90% of all Caucasian RA patients carry such an HLA-DRB1 marker with “shared epitope”. Detection of these alleles are associated with a four times higher risk of developing RA and at an early stage can be helpful for establishing a diagnosis. Moreover, SE alleles are prognostic markers for the course and the severity of the disease. Patients who carry two of the RA-associated SE alleles tend to suffer from a more severe course and a faster progression than patients with only one or no SE allele at all. In addition, the presence of SE alleles may have an impact on the success of different treatments.

Other prognostic makers for RA are interleukin 4 (IL4) and the IL4 receptor (IL4R). Certain genetic variants in the IL4R gene occur more frequently in patients with a progressive bone destruction than in patients with a mild course of the disease. The allele variant IL4R-I50V has been associated with erosions occurring already within 2 years after onset of the disease.