Autoantibodies detectable in the sera of silicosis patients. The relationship between the anti-topoisomerase I antibody response and HLA-DQB1*0402 allele in Japanese silicosis patients.

Eighty-one Japanese silicosis patients and 66 healthy volunteers were analyzed for autoantibodies by ELISA, and HLA-genotyping using the PCR-RFLP method was performed. Anti-topoisomerase I (anti-topo I) autoantibodies were detected in seven patients without any clinical features of autoimmune diseases such as progressive systemic sclerosis (PSS), although anti-topo I have been mostly reported in PSS patients. Antibodies directed to RNP, ssDNA, dsDNA and cent-B were not detected among the anti-topo I positive patients. The indirect immunofluorescent staining pattern of Hep-2 cells with the sera of anti-topo I positive silicosis patients demonstrated the typical mode of anti-topo I autoantibodies observed in the patients with PSS. The allelic frequency of HLA-DQB1*0402 was significantly higher in anti-topo I positive patients (28.6%) than in anti-topo I negative patients (1.5%, P < 0.001) or healthy controls (0.8%, P<0.001). HLA-DQB1*0301, DQB1*0601 and DPB1*1801 alleles were more frequently detected in anti-topo I positive patients than in the patients without anti-topo I or in healthy volunteers, but no significant difference was observed. DQB1 allele is associated with the induction of anti-topo I autoantibodies in Japanese silicosis patients, but the allele is not the same as in Caucasian PSS patients. Another allele (DQB1*0402) plays an important role in Japanese silicosis patients. The most important factor to induce anti-topo I autoantibodies seems not to be the type of alleles themselves, but the position of some specific amino acid residues in the DQ beta first domain. These findings will be useful for preventing occupational autoimmune diseases.