A model for the role of HLA-DQ molecules in the pathogenesis of juvenile chronic arthritis |
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Authors: | J. P. Haas A. Andreas B. Rutkowski H. Brunner E. Keller J. Hoza S. Havelka G. Sierp E. D. Albert |
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Affiliation: | (1) Labor für Immungenetik, Kinderpoliklinik der Universität, Pettenkoferstrasse 20 a, W-8000 München 2, Germany;(2) Chidren's Hospital, Charles University, Prague, Czecho-Slovakia;(3) Research Institute of Rheumatology, Charles University, Prague, Czecho-Slovakia |
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Abstract: | Summary Restriction fragment length polymorphism (RFLP) typing of MHC-class II loci DRB, DQA1, DQB1, DQA2 and DPB1 was performed in 94 patients with seronegative juvenile chronic arthritis (JCA) and 184 random controls. Analysis of allele frequencies and MHC-class II 4-loci haplotypes indicate: (1) Susceptibility to JCA is more strongly associated with the HLA-DQ subregion than with the HLA-DR subregion, especially in early onset pauciarticular JCA (EOPA-JCA). (2) Haplotype and sequence analysis show two independent MHC-class II associations for susceptibility to EOPA-JCA, one located in DQA1, the other in DPB1. (3) Two RFLP defined patterns of the DQA1 locus, DQA1.5 (DQA1*0501) and DQA1.8 (DQA1*0401, *0601) are strongly associated with the disease. (4) Analysis of amino-acid (AA) sequences coded in exon 2 of DQA1 reveals an AA sequence of six AAs common to all three associated DQA1 alleles. This suggests a model that includes a functional role for HLA-DQ molecules in the pathogenesis of JCA.Most of the data covered in this article are from the doctoral thesis of Haas [39]. Supported by SFB 217 To whom ffprint requests should be sent |
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Keywords: | Juvenile chronic arthritis MHC-class II association HLA-DQ molecules Restriction fragment length polymorphism Arthritogenic peptide |
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