Different distribution of HLA class II alleles in anti-topoisomerase I autoantibody responders between silicosis and systemic sclerosis patients, with a common distinct amino acid sequence in the HLA-DQB1 domain.
Autoantibodies against DNA topoisomerase I (anti-topo I) have been reported to be specific to systemic sclerosis (SSc), however, anti-topo I was detected in patients with silicone breast implants, SLE without features of SSc, and rheumatic diseases. We detected anti-topo I positive silicosis patients without any symptoms of autoimmune diseases. The correlation between anti-topo I autoantibody responses and HLA class II has been established. HLA-DRB1*1502; DQB1*0601 has been reported to be the most frequent anti-topo I associated haplotype among Japanese SSc patients. In this study, haplotype HLA-DR15; DQ6 was detected in all 4 anti-topo I positive Asian Japanese SSc patients randomly selected. Furthermore, HLA-DQB1*0402 was identified in 3 of 4 anti-topo I positive silicosis patients. These findings coincide with the results of a previous study, in which all 4 Japanese patients with anti-topo I had the DQB1*04 alleles, whereas no studies among Caucasian-Americans, African-Americans and Choctaw Indians found the involvement of DQB1*04. We investigated common features among various DQB 1 alleles. HLA-DQB I with a distinct characteristic is clearly involved in the anti-topo I response irrespective of ethnic groups, the main disease, or silica exposure. A common positioning of distinct amino acids, (i.e. positions 14, 30, 57 and 77 of the DQbeta1 domain are methionine, tyrosine, aspartic acid and threonine, respectively,) seems to be associated with anti-topo I response. The above-mentioned amino acid sequence is detected in alleles *0301, *0303, *0306, *0401, *0402, *0601 and *0602.
Ueki
A
A
Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan. aueki@med.kawasakim.ac.jp
Isozaki
Y
Y
Tomokuni
A
A
Ueki
H
H
Kusaka
M
M
Tanaka
S
S
Otsuki
T
T
Sakaguchi
H
H
Hyodoh
F
F
D000483:Alleles; D000595:Amino Acid Sequence; D000596:Amino Acids; D001323:Autoantibodies / Q000276:immunology*; D004264:DNA Topoisomerases, Type I / Q000276:immunology*; D005802:Genes, MHC Class II; D006682:HLA-DP Antigens / Q000235:genetics / Q000276:immunology; D059868:HLA-DP beta-Chains; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology; D012829:Silicosis / Q000235:genetics* / Q000276:immunology; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D001323:Autoantibodies; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D004264:DNA Topoisomerases, Type I