HLA-DPB1 associations differ between DRB1*03 positive anti-Jo-1 and anti-PM-Scl antibody positive idiopathic inflammatory myopathy.
OBJECTIVE
The HLA 8.1 ancestral haplotype (HLA-B*08/DRB1*03/DQA1*05/DQB1*02) is associated with adult/juvenile idiopathic inflammatory myopathy (IIM), but confers a greater strength of association in patients possessing anti-Jo-1 or anti-PM-Scl antibodies. The HLA-DPB1 gene is centromeric to other HLA class II loci and separated by a recombination hotspot. We investigated whether HLA-DPB1 associations differ between anti-Jo-1 and anti-PM-Scl antibody-positive IIM cases.


METHODS
Two hundred and thirty-three adult IIM patients (73% females, 49.4 +/- 13.6 years) with PM (n = 89), DM (n = 88) and myositis associated with another CTD (n = 55) and 85 juvenile DM patients (75% females, 6.2 +/- 3.6 years) were compared with 678 UK Caucasian controls. Patients/controls were genotyped for HLA-DPB1 and DRB1 alleles. Myositis-specific and associated antibodies were identified in cases using immunoprecipitation.


RESULTS
HLA-DPB1*0101 was associated with IIM overall [22 vs 13% controls, corrected probability (P(corr)) = 2 x 10(-03); odds ratio (OR) 2.0; 95% CI 1.4, 2.9], PM (P(corr) = 7 x 10(-03); OR 2.5; 95% CI 1.5, 4.4) and anti-Jo-1 (P(corr) = 3 x 10(-5); OR 4.1; 95% CI 2.1, 7.8). No significant DPB1*0101 difference was present between anti-PM-Scl cases and controls. The HLA-DPB1*0101 association in IIM overall cases was dependent on the presence of DRB1*03. A number of HLA-DRB1*03/DPB1 haplotypes were identified, but only DRB1*03/DPB1*0101 was associated with anti-Jo-1 antibody-positive cases.


CONCLUSIONS
The HLA-DRB1*03/DPB1*0101 haplotype is a risk factor for anti-Jo-1 antibody-positive IIM. Thus, although DRB1*03 is strongly associated with possession of either anti-Jo-1 or anti-PM-Scl, differing antibody associations are observed at the HLA-DPB1 locus.
Chinoy
Hector
H
Centre for Integrated Genomic Medical Research, University of Manchester, UK.
Payne
Debbie
D
Poulton
Kate V
KV
Fertig
Noreen
N
Betteridge
Zoe
Z
Gunawardena
Harsha
H
Davidson
Joyce E
JE
Oddis
Chester V
CV
McHugh
Neil J
NJ
Wedderburn
Lucy R
LR
Ollier
William E
WE
Cooper
Robert G
RG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005095:Exoribonucleases / Q000276:immunology*; D063326:Exosome Multienzyme Ribonuclease Complex; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006682:HLA-DP Antigens / Q000235:genetics*; D059868:HLA-DP beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009220:Myositis / Q000235:genetics* / Q000276:immunology; D009687:Nuclear Proteins / Q000276:immunology*; D055815:Young Adult
D000974:Antibodies, Antinuclear; D015415:Biomarkers; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C046750:Jo-1 antibody; D009687:Nuclear Proteins; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C077044:EXOSC10 protein, human