C4A and C4B null alleles are genetic markers of different types of systemic sclerosis in Japanese patients

Clin Exp Rheumatol. 1998 Jan-Feb;16(1):55-60.


Objective: The contribution of the polymorphism of complement C4A and C4B alleles to the pathogenesis of systemic sclerosis (SSc) was studied in Japanese patients.

Methods: C4A and C4B typing was carried out in 44 SSc patients and in 83 normal subjects using electrophoresis followed by immunofixation and immunoblotting. HLA-DR typing and HLA DRB1*15 and *08 genotyping were carried out by the PCR method and the PCR-SSCP method, respectively.

Results: In SSc with diffuse scleroderma, the frequency of C4BQ0 was significantly increased (44.4%, p < 0.001, pc < 0.01). In SSc with antitopoisomerase I antibody (a-Scl-70) C4BQ0 was also increased (50.0%, p < 0.001, pc < 0.01). Association analysis indicated that the increase in C4BQ0 was not primary but reflected an increase in HLA-DRB1*1502. In contrast, C4A/Q0 was significantly increased in limited scleroderma (53.8%, p < 0.005, pc < 0.05) and SSc without a-SCL-70 (53.8%, p < 0.005, pc < 0.05).

Conclusion: Diffuse scleroderma with SSC with a-Scl-70 have different genetical backgrounds from limited scleroderma and SSc without a-Scl-70, respectively, in Japanese patients. C4AQ0 were independent genetic markers for each clinical subgroup and for a a-Scl-70 positivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Complement C4a / genetics*
  • Complement C4b / genetics*
  • Female
  • Genetic Markers
  • HLA-DR Antigens / genetics
  • HLA-DR Serological Subtypes
  • HLA-DRB1 Chains
  • Histocompatibility Testing
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic
  • Scleroderma, Systemic / genetics*
  • Scleroderma, Systemic / immunology*


  • Genetic Markers
  • HLA-DR Antigens
  • HLA-DR Serological Subtypes
  • HLA-DR15 antigen
  • HLA-DR16 antigen
  • HLA-DR8 antigen
  • HLA-DRB1 Chains
  • Complement C4a
  • Complement C4b