Clinical, immunologic, and genetic features of familial systemic sclerosis

Abstract

Objective. To examine whether the affected firstdegree 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 firstdegree 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.

Association of TNFSF4 (OX40L) polymorphisms with susceptibility to systemic sclerosis

“…All patients with SSc fulfilled American College of Rheumatology (ACR) preliminary criteria for disease classification28 or had at least three of the five CREST (for ‘Calcinosis, Raynaud’s phenomenon, Eesophageal dysfunction, Sclerodactyly and Telangiectasias') features 29 30. Patients were not excluded if they had symptoms of myositis or Sjogren's syndrome.…”

Unfolding the pathogenesis of scleroderma through genomics and epigenomics

“…This is supported by the higher familial relative risk of the disease itself or autoimmune diseases [4, 8], low disease concordance but high concordance of autoantibodies produced in monozygotic twins [5], and multi-case SSc families that are concordant for SSc-specific autoantibodies as well as human leukocyte antigen (HLA) haplotypes [9]. Twin studies have been performed in several autoimmune diseases.…”

Unraveling the genetic component of systemic sclerosis

“…Interestingly, twin-studies revealed a high concordance of autoantibody production in monozygotic twins (FeghaliBostwick et al 2003), familial relative risks in SSc patient Wrst-degree relatives is 13-fold higher than in the general population, and 15-fold higher in siblings (Arnett et al 2001), and multi-case SSc families are concordant for autoantibody production and HLA-haplotypes (Assassi et al 2007). Hence, considering all supporting evidence for the contribution of genetic factors to the disease, SSc was deWned as a complex disease in which genetic susceptibility J. E. Martín · L. Bossini-Castillo · J. Martín (&) Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Consejo Superior de Investigaciones CientíWcas, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento s/n 18100-Armilla, Granada, Spain e-mail: martin@ipb.csic.es and diVerent environmental triggers interact both in the pathogenesis and in the prognosis of the disease (Gabrielli et al 2009).…”