Clinical, immunologic, and genetic features of familial systemic sclerosis

Arthritis Rheum. 2007 Jun;56(6):2031-7. doi: 10.1002/art.22647.

Abstract

Objective: To examine whether the affected first-degree relatives within multicase systemic sclerosis (SSc; scleroderma) families are concordant for autoantibody profile, disease type, and HLA class II haplotypes and whether clinical expression and serologic characteristics of familial SSc differ from those of sporadic SSc.

Methods: Seven hundred ten SSc families from the Scleroderma Family Registry and DNA Repository (Scleroderma Registry) were examined, and 18 multicase families were identified. SSc cases and their first-degree family members underwent serologic testing for different autoantibodies. The disease type and various disease features were abstracted from the available medical records. Additionally, HLA class II typing was performed on the multicase SSc sibpairs.

Results: The observed SSc-specific antibody concordance within each multicase SSc family was statistically more common than expected by chance alone (P = 0.007). The autoantibody profile and disease features of familial and sporadic SSc cases did not differ significantly. The frequency of autoantibody positivity was not different between unaffected first-degree family members of patients from multicase versus singleton SSc families. HLA haplotype sharing between SSc sibpairs was significantly more common than expected (P = 0.011).

Conclusion: The affected members within multicase SSc families tend to be concordant for SSc-specific autoantibodies and HLA haplotypes; familial SSc does not appear to be a unique disease subset.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Autoantibodies / genetics
  • Autoantibodies / metabolism*
  • DNA / genetics
  • Family
  • Female
  • Haplotypes
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology*
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Registries
  • Scleroderma, Systemic / genetics*
  • Scleroderma, Systemic / immunology*
  • Scleroderma, Systemic / physiopathology

Substances

  • Autoantibodies
  • Histocompatibility Antigens Class II
  • DNA