Susceptible and protective major histocompatibility complex class II alleles in early-onset pauciarticular juvenile chronic arthritis.
Oligonucleotide typing for alleles of the MHC loci DRB1, DQA1, and DQB1 was performed in 160 patients suffering from EOPA, JCA (or JRA = juvenile rheumatoid arthritis). Allele and haplotype frequencies of the patients were compared with the data of an unrelated healthy control group consisting of 200 individuals. Analysis of frequencies shows that HLA alleles are associated not only with susceptibility to EOPA-JCA but also with protection from the disease. The presence of protection connected with certain HLA alleles was assessed using a calculation which takes into account the condition that if one allele is increased, all other alleles of the same locus must be decreased in compensation. Protection can be assumed only in cases where a given allele has an observed frequency which is significantly beyond the expected compensatory decrease. Thus a hierarchy of associations was observed in EOPA-JCA patients. The alleles of the haplotypes DRB1*11 (12)-DQA1*0501-DQB1*0301 as well as DRB1*08-DQA1*0401-DQB1*0402 were found to be associated with susceptibility to disease, whereas the alleles DRB1*07 and DQA1*0201 converge with significant protection from the disease. Whereas the association with disease susceptibility seems to depend on a sequence motif encoded in certain DQA1 alleles, protection is associated either with alleles of DRB1 or DQA1.
Haas
J P
JP
Immunogenetics Laboratory Children's LMU Polyclinic, Munich, Germany.
Nevinny-Stickel
C
C
Schoenwald
U
U
Truckenbrodt
H
H
Suschke
J
J
Albert
E D
ED
D000483:Alleles; D000595:Amino Acid Sequence; D001171:Arthritis, Juvenile / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D001483:Base Sequence; D002648:Child; D006681:HLA-D Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data
D006681:HLA-D Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens