HLA-DRB1 Shared epitope |
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| Nomenclature of the HLA-DR
Alleles The MHC class ll are cell surface molecules which perform an essential function in immunological detection using T-helper cells. They are encoded by the genes HLA-DR, -DQ and -DP. Each MHC molecule consists of a a- and a b-chain. In the case of the DR molecule, the two chains are encoded by the genes HLA-DRA und HLA-DRB1; only DRB1 is polymorph i.e. only this gene has a number of different alleles existing in the population. In addition, each individual possesses two DRB1 alleles, one from each parent. The serological typification of the DR alleles leads to the differentiation between 10 different classes, HLA-DR1-DR10. Molecular genetic typification shows that these classes can be further split e.g. DR2 has deen divided into DR15 and DR16. Within these classes it is possible to distinguish between a number of subtypes. Up until now, 33 subtypes of DR4 have been described, and are termed HLA-DRB1*0401-*0433. |
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| Clinicale relevance of
the shared epitope Rheumatoid arthritis (RA) or chronic polyarthritis is an intermittent systemic autoimmune disease which occurs in approx. 1% of the population. The aetiology of the disease is unknown. It has been shown for some time by numerous studies that there is a genetic disposition for RA caused by several alleles of the HLA-DRB1 region. RA is associated with the HLA- DRB1*04 subtypes DRB1*0401, *0404, *0405, *0408 and also, in some different ethnic groups with the subtypes DRB1*0101, *0102 and DRB1*1001. All RA-associated HLA-DRB1 alleles encode in their third hypervariable region, at postion 70-74, the amino acids QKRAA (*0401), QRRAA (*0404, *0405, *0408, *0101, *0102) or RRRAA (*1001). This so-called rheumatoid epitope or shared epitope can be found in approximately 80-90% of all Caucasian RA patients. It is not known how the shared epitope in HLA-DRB1*04 supports the development of RA. Tests show that, alongside the higher risk of RA, the shared epitope can also be a prognostic marker for the clinical course and severity of the disease. In addition to this, numerous studies have shown a gene-dose effect. Patients homozygous for the shared epitope have more often a more severe course of disease than those with only one shared epitope allele (see chart). |
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| Chart changed from Internist 40: 922-929 (1999) Infection with the spirochete Borrelia burgdorferi causes Lyme disease. Roughly 10% of the patients develop a antibiotic treatment-resistant Lyme arthritis. People with the shared epitope QKRAA allels of the HLA-DRB1*04 group are also genetically predisposed to this kind of arthritis. Typing of the shared epitope in the HLA-DRB1 alleles seems necessary to
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| References Weyand CM et al. (1995) Inherited and noninherited risk factors in rheumatoid arthritis Curr Opin in Rheumatol 7: 206-213 Nepom GT et al. (1996) Prognostic implications of HLA genotyping in the early assessment of patients with rheumatoid arthritis J Rheumatol Suppl 44: 5-9 Wagner U et al. (1997) HLA markers and prediction of clinical course and outcome in rheumatoid arthritis Arthritis and Rheumatism 40: 341-351 Perdriger A et al. (1997) Role of HLA-DR-DR and DR-DQ Associations in the Expression of Extraarticular Manifestations and Rheumatoid Factor in Rheumatoid Arthritis J Rheumatol 24: 1272-1276 Stavropoulos C et al. (1997) HLA-DRB1 allels in Greek rheumatoid arthritis patients and their association with clinical characteristics Eur J Immunogenet 24: 265-274 Rowley MJ et al. (1997) The Effect of HLA-DRB1 Disease Susceptibility Markers on the Expression of RA Scand J Rheumatol 26: 448-455 O�Dell JR et al. (1998) HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments Ann Rheum Dis 57: 209-213 Reveille JD (1998) The genetic contribution to the pathogenesis of rheumatoid arthritis Curr Opin Rheumatol 10: 187-200 Istanbul rheumatology study group (1998) Shared epitope �homozygosity� is strongly associated with rheumatoid arthritis in Turkey British J of Rheumatology 37: 1126-1128 Toussirot E et al. (1999) HLA-DRB1 Alleles and Shared Amino Acid Sequences in Disease Susceptibility and Severity in Patients from Eastern France with Rheumatoid Arthritis J of Rheumatol 26: 1446-1451 Valenzuela A et al. (1999) Association of HLA shared epitope with joint damage progression in rheumatoid arthritis Hum Immunol 60: 250-254 Meyer MJ et al. (1999) HLA-DRB1 Genotype Influences Risk for and Severity of Rheumatoid Arthritis J Rheumatol 26: 1024-1034 Nitzsche et al. (1999) Entz�ndungsmechanismen bei rheumatoider Vaskulitis und Riesenzellarteriitis Internist 40: 922-929 >> Principles of the test >> Examples for the detection |
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