Genetische Diagnostik in der Rheumatologie

Zusammenfassung

Autoimmunologische Prozesse und insbesondere häufige rheumatische Erkrankungen wie die rheumatoide Arthritis (RA) und die Gruppe der Spondyloarthritiden (SpA) weisen einen mittlerweile gut charakterisierten genetischen Hintergrund auf. Die genetische Charakterisierung dieser Erkrankungen hat einen wesentlichen Beitrag dazu geleistet, pathogenetische Modelle für sie zu entwickeln. Der vorliegende Artikel gibt einen Überblick über genetische Marker in der rheumatologischen Labordiagnostik.

Abstract

Different autoimmune diseases exhibit a well characterised genetic background. Thus, genetic approaches have helped strongly to elucidate pathogenetic models for rheumatic diseases like rheumatoid arthritis (RA) or spondyloarthritis (SpA). This review summarises the applicability of genetic diagnostics in the field of rheumatological laboratory diagnostics.

Schlüsselwörter

Rheumatoide Arthritis - Spondyloarthritis - Genetik - Diagnostik

Key words

rheumatoid arthritis - spondyloarthritis - genetics - diagnostics

• Literatur

• 1 The Wellcome Trust Case Control Consortium . Genome-wide association study of 14 000 cases of seven common diseases and 3 000 shared controls. Nature 2007; 447: 661-678
• 2 Almeida de Jesus A, Goldbach-Mansky R. Monogenic autoinflammatory diseases: concept and clinical manifestations. Clin Immunol 2013; 147: 155-174
• 3 de Vries N, van Riel PL, van de Putte LB. Research in complex diseases. Lancet 2002; 359: 1243-1245
• 4 Stastny P. Mixed lymphocyte cultures in rheumatoid arthritis. J Clin Invest 1976; 57: 1148-1157
• 5 Stastny P, Fink CW. HLA-Dw4 in adult and juvenile rheumatoid arthritis. Transplant Proc 1977; 9: 1863-1866
• 6 Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 1987; 30: 1205-1213
• 7 Harrison B, Thomson W, Symmons D et al. The influence of HLA-DRB1 alleles and rheumatoid factor on disease outcome in an inception cohort of patients with early inflammatory arthritis. Arthritis Rheum 1999; 42: 2174-2183
• 8 Cordonnier C, Meyer O, Palazzo E et al. Diagnostic value of anti-RA33 antibody, antikeratin antibody, antiperinuclear factor and antinuclear antibody in early rheumatoid arthritis: comparison with rheumatoid factor. Br J Rheumatol 1996; 35: 620-624
• 9 Schellekens GA, de Jong BA, van den Hoogen FH et al. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest 1998; 101: 273-281
• 10 Klareskog L, Ronnelid J, Lundberg K et al. Immunity to citrullinated proteins in rheumatoid arthritis. Annu Rev Immunol 2008; 26: 651-675
• 11 Kallberg H, Padyukov L, Plenge RM et al. Gene-Gene and Gene-Environment Interactions Involving HLA-DRB1, PTPN22, and Smoking in Two Subsets of Rheumatoid Arthritis. Am J Hum Genet 2007; 80: 867-875
• 12 Scherer HU, van der Linden MP, Kurreeman FA et al. Association of the 6q23 region with the rate of joint destruction in rheumatoid arthritis. Ann Rheum Dis 2010; 69: 567-570
• 13 van der Linden MP, Feitsma AL, le Cessie S et al. Association of a single-nucleotide polymorphism in CD40 with the rate of joint destruction in rheumatoid arthritis. Arthritis Rheum 2009; 60: 2242-2247
• 14 Hoppe B, Haupl T, Egerer K et al. Influence of peptidylarginine deiminase type 4 genotype and shared epitope on clinical characteristics and autoantibody profile of rheumatoid arthritis. Ann Rheum Dis 2009; 68: 898-903
• 15 Suzuki T, Ikari K, Yano K et al. PADI4 and HLA-DRB1 are genetic risks for radiographic progression in RA patients, independent of ACPA status: results from the IORRA cohort study. PloS one 2013; 8: e61045
• 16 Prots I, Skapenko A, Wendler J et al. Association of the IL4R single-nucleotide polymorphism I50V with rapidly erosive rheumatoid arthritis. Arthritis Rheum 2006; 54: 1491-1500
• 17 Ellervik C, Birgens H, Tybjaerg-Hansen A et al. Hemochromatosis genotypes and risk of 31 disease endpoints: meta-analyses including 66 000 cases and 226 ,000 controls. Hepatology 2007; 46: 1071-1080
• 18 Allen KJ, Gurrin LC, Constantine CC et al. Iron-overload-related disease in HFE hereditary hemochromatosis. N Engl J Med 2008; 358: 221-230
• 19 Khan MA. Thoughts concerning the early diagnosis of ankylosing spondylitis and related diseases. Clinical and experimental rheumatology 2002; 20: S6-S10
• 20 Braun J, Sieper J. Ankylosing spondylitis. Lancet 2007; 369: 1379-1390
• 21 van Gaalen FA, Verduijn W, Roelen DL et al. Epistasis between two HLA antigens defines a subset of individuals at a very high risk for ankylosing spondylitis. Ann Rheum Dis 2013; 72: 974-978