HLA-DP/DR interaction in early onset pauciarticular juvenile chronic arthritis.
We investigated the polymorphic second exon of the HLA-DPB1 and HLA-DRB1 genes, using in vitro DNA amplification by polymerase chain reaction (PCR) and oligonucleotide hybridization in 136 patients with early onset pauciarticular juvenile chronic arthritis (EOPA-JCA) and 199 healthy controls. The analysis of the HLA-DRB1 system revealed that most of the DRB1 alleles are not indifferent with respect to susceptibility to EOPA-JCA. There is a hierarchy of susceptible (DRB1*08, DR5), "permissive" (DRB1*01), moderately "protective" (DR2, DRB1*04), and "protective" (DRB1*07) alleles. In contrast, no hierarchy could be shown for the HLA-DPB1 system. DPB1*0201 was found to be susceptible. The relatively frequent alleles DPB1*0402 and DPB1*0401 seem to be indifferent. The associations with DPB1*0201, DR5, and DRB1*08 are independent of each other: that is to say they, are not brought about by linkage disequilibrium. The susceptible alleles DPB1*0201 and DR5 show evidence for interaction in the pathogenesis of EOPA-JCA. Interaction seems likely between DPB1*0201 and DRB1*08, DR5 and DRB1*08, or between DR6 and DRB1*08. The strongest interaction exists between DPB1*0201 and a common DQ factor associated with both DR5 and DRB1*08. Finally, we observed a hierarchy among the various marker combinations, where the risk of developing EOPA-JCA increases with the number of associated markers present in an individual.
Paul
C
C
Immunogenetics Laboratory, University of Munich, Germany.
Schoenwald
U
U
Truckenbrodt
H
H
Bettinotti
M P
MP
Brünnler
G
G
Keller
E
E
Nevinny-Stickel
C
C
Yao
Z
Z
Albert
E D
ED
D000483:Alleles; D001171:Arthritis, Juvenile / Q000235:genetics*; D001483:Base Sequence; D005787:Gene Frequency; D006682:HLA-DP Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry
D006682:HLA-DP Antigens; D006684:HLA-DR Antigens; D009838:Oligodeoxyribonucleotides