Association of human leukocyte antigen class II genes with autoantibody profiles, but not with disease susceptibility in Japanese patients with systemic sclerosis

Masataka Kuwana, Hidetoshi Inoko, Hideto Kameda, Takaki Nojima, Shinji Sato, Kunio Nakamura, Takashi Ogasawara, Michito Hirakata, Yasuo Ohosone, Junichi Kaburaki, Yutaka Okano, Tsuneyo Mimori

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Abstract

Object: To examine the role of human leukocyte antigen (HLA) class II genes in the development of systemic sclerosis (SSc) as well as in the clinical and serologic expression of SSc in patients. Methods: HLA-DRB1, DRB3, DRB4, DQB1, and DPB1 alleles were determined by genotyping; and serum antinuclear antibodies were identified using indirect immunofluorescence, double immunodiffusion and immunoprecipitation. Patients: One hundred and five Japanese patients with SSc and 104 race-matched healthy controls. Results: Frequencies of DRB1 and DQB1 alleles were not different between SSc patients and healthy controls, while DPB1*0901 was marginally increased in SSc patients. In contrast, SSc-related autoantibodies were closely associated with the clinical features. HLA class II genes were detected as follows: anti-DNA topoisomerase I antibody with diffuse cutaneous involvement, pulmonary fibrosis, and DRB1*1502-DQB1*0601-DPB1*0901; anti-U1RNP antibody with overlapping features of lupus and/or myositis and DRB1*0401/*0802-DQB1*0302; and anticentromere antibody with limited cutaneous involvement and DRB1*0101-DQB1*0501-DPB1*0402. In the analysis of the association of HLA class II and the clinical features in SSc patients significant differences were obtained only for the increased frequencies of arthritis and rheumatoid factor in patients with DRB1*0405 compared to those without. Conclusion: HLA class II genes strongly influence the production of SSc-related autoantibodies rather than the development of SSc. In addition, SSc is a composite disease of distinctive subsets defined by serum autoantibodies, which have specific clinical and HLA class II associations.

Original languageEnglish
Pages (from-to)336-344
Number of pages9
JournalInternal Medicine
Volume38
Issue number4
DOIs
Publication statusPublished - 1999 Apr

Keywords

  • Antinuclear antibody
  • Haplotype
  • Major histocompatibility complex
  • Scleroderma

ASJC Scopus subject areas

  • Internal Medicine

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    Kuwana, M., Inoko, H., Kameda, H., Nojima, T., Sato, S., Nakamura, K., Ogasawara, T., Hirakata, M., Ohosone, Y., Kaburaki, J., Okano, Y., & Mimori, T. (1999). Association of human leukocyte antigen class II genes with autoantibody profiles, but not with disease susceptibility in Japanese patients with systemic sclerosis. Internal Medicine, 38(4), 336-344. https://doi.org/10.2169/internalmedicine.38.336