HLA-DRB1 polymorphisms and autoimmune responses to desmogleins in Japanese patients with pemphigus

Sachiko Miyagawa, M. Amagai, H. Niizeki, Y. Yamashina, T. Kaneshige, T. Nishikawa, T. Shirai, H. Inoko

研究成果: Article査読

38 被引用数 (Scopus)

抄録

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are caused by autoantibodies against keratinocyte adhesion molecules desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1), respectively. To determine possible major histocompatibility complex (MHC) class II associations with autoantibody responses to desmogleins, haplotype and allele distributions, along with molecular polymorphisms of HLA-DR and -DQ genes were analyzed based on the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) results in 85 Japanese patients with pemphigus. Each of 55 PV patients carried at least one allele of HLA-DRB1(*)04 and DRB1(*)14 subtypes, with significant increases of HLA-DRB1(*)0406/DQA1(*)0301/DQB1(*)0302, DRB1(*)14/DQA1(*)0104/DQB1(*)05 and DRB1(*)1406/DQA1(*)0503/DQB1*0301 haplotypes compared to normal controls. The HLA-DRB1(*)04 and DRB1(*)14 alleles carried by PV patients shared hydrophobic amino acid residues Phe26, Leu67 and Val86, as well as hydrophilic amino acid residues at positions 70 and 71 on the DRB1 beta chain. HLA-DR/DQ distributions did not differ among PV patients according to the presence or absence of anti-Dsg1 co-existing with anti-Dsg3. Thirty PF patients, all producing autoantibodies only to Dsg1, showed more diverse HLA-DR/DQ distributions, sharing hydrophobic amino acid residues at positions 26 and 67, as well as hydrophilic amino acid residues at positions 70 and 71, of the DRB1 chain. These findings suggest that autoantibody responses to desmogleins might be regulated by amino acid residues at positions 26, 67, 70, 71 and 86 at peptide binding sites HLA-DRB1 molecules, and that autoimmune responses to Dsg3 might be more strictly regulated by specific amino acid residues at these positions on the HLA-DRB1 chain than responses to Dsg1.

本文言語English
ページ(範囲)333-340
ページ数8
ジャーナルTissue Antigens
54
4
DOI
出版ステータスPublished - 1999 10 26

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Genetics

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