HLA-D region genes associated with autoantibody responses to histidyl-transfer RNA synthetase (Jo-1) and other translation-related factors in myositis.
Myositis has been associated with HLA-B8 and DR3, especially in white patients with polymyositis and serum anti-Jo-1 antibodies. Twenty-eight patients with myositis and serum translation-related autoantibodies anti-Jo-1, anti-PL-7, anti-PL-12, anti-KJ, and anti-SRP were studied for HLA class II specificities by Southern blotting with HLA-DR beta, DQ beta, and DQ alpha probes. The association of HLA-DR3 (DRw17) with anti-Jo-1 antibodies in white myositis patients was confirmed (P = 0.003, relative risk 8.9). However, HLA-DRw52 haplotypes, regardless of subtype, were present in all of the white and black patients with serum anti-Jo-1 and other translation-related autoantibodies. Moreover, one anti-Jo-1 positive patient had HLA-DRw8, an HLA-DRw52 haplotype on which the DR beta 3 gene has been partially deleted. No HLA-DQ specificity or allele was common to all patients. The HLA-DR3, DR5, DRw6, and DRw8 haplotypes, which bear the HLA-DRw52 specificity, share the most homology in the DR beta 1 first hypervariable region at amino acid positions 9-13. Thus, this DR beta 1 region appears to be the most likely candidate "epitope" for translation-related autoimmune responses in inflammatory myositis.
Goldstein
R
R
Department of Internal Medicine, University of Texas Health Science Center, Houston 77225.
Duvic
M
M
Targoff
I N
IN
Reichlin
M
M
McMenemy
A M
AM
Reveille
J D
JD
Warner
N B
NB
Pollack
M S
MS
Arnett
F C
FC
D000483:Alleles; D000604:Amino Acyl-tRNA Synthetases / Q000276:immunology*; D000974:Antibodies, Antinuclear / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D044383:Black People; D005796:Genes; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006643:Histidine-tRNA Ligase / Q000276:immunology*; D006801:Humans; D009220:Myositis / Q000208:ethnology / Q000235:genetics / Q000276:immunology*; D012150:Polymorphism, Restriction Fragment Length; D014176:Protein Biosynthesis / Q000276:immunology; D044465:White People
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; C046750:Jo-1 antibody; D000604:Amino Acyl-tRNA Synthetases; D006643:Histidine-tRNA Ligase