Familial Clustering of Auto-immune Diseases in Patients with Systemic Sclerosis

Background The emerging concept of shared auto-immunity suggests that certain genes predispose to various autoimmune diseases. Hence, well-known disease phenotypes may be related by common underlying genotypes. We undertook to determine whether we could find evidence of shared auto-immunity in patients with systemic sclerosis (SSc).
Methods The study subjects consisted of those enrolled in the Canadian Scleroderma Research Group (CSRG) Registry. All patients in this Registry have SSc diagnosed by a rheumatologist. The patients undergo standardized history and physical examination and data on over 1000 variables are collected. In the detailed case report forms, patients are asked about family history of SSc and other auto-immune diseases in their parents, siblings, children, grand-parents, aunts, uncles and cousins. The rates of auto-immune diseases were computed by patient, such that a patient who reported a disease in several family members was nevertheless counted only once. The frequency of reports of disease in several family members when counted separately was also computed.
Results This study included 352 SSc patients (88% women, 88% white, mean age 56 (± 13) years, mean disease duration 11 (± 9) years). Patients reported a high prevalence of SSc and other auto-immune diseases in relatives. The proportion of patients who reported the following autoimmune diseases in either a parent or a sibling were: SSc 2.3%, systemic lupus erythematosus (SLE) 5.1%, rheumatoid arthritis (RA) 28.7%, polymyositis/dermatomyositis (PM/DM) 2.0 %, Sjogren’s syndrome (SjS) 0.6%, mixed connective tissue disease (MCTD) 0.9% and auto-immune thyroid disease 15.6%. When children and second-degree relatives were included, the rates were: SSc 4.5%, SLE 8.5%, RA 39.2%, PM/DM 2.0%, SjS 1.1%, MCTD 1.1% and auto-immune thyroid disease 21.3%. The absolute number of relatives of patients with SSc with an auto-immune disease was also very high. The patients reported the following numbers of affected family members: SSc 22, SLE 41, RA 287, PM/DM 14, SjS 4, MCTD 9 and auto-immune thyroid disease 162.
Conclusion The high prevalence of other auto-immune diseases in families of SSc patients strongly suggests that there may be one shared gene or group of genes that predisposes to multiple autoimmune diseases. The factors that determine whether someone with this predisposition will develop one specific disease or another may then depend upon the presence of either other genetic factors or specific environmental triggers. Research to identify the common genetic determinants of auto-immune diseases may, in the future, dramatically change the way autoimmune diseases are classifed. It may also provide insight into the pathogenesis of these diseases and targets for new therapeutic interventions.

 M. Hudson, None; M. Baron, None.