A model for the role of HLA-DQ molecules in the pathogenesis of juvenile chronic arthritis.
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.
Labor für Immungenetik, Kinderpoliklinik der Universität, München, Federal Republic of Germany.
J P
JP
Haas
A
A
Andreas
B
B
Rutkowski
H
H
Brunner
E
E
Keller
J
J
Hoza
S
S
Havelka
G
G
Sierp
E D
ED
Albert
D000483:Alleles; D000595:Amino Acid Sequence; D001171:Arthritis, Juvenile / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D002648:Child; D004198:Disease Susceptibility; D006683:HLA-DQ Antigens / Q000032:analysis / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
D006683:HLA-DQ Antigens