title: Familial aggregation of autoimmune disease in juvenile dermatomyositis.
abstract: OBJECTIVE
  Familial aggregation of autoimmune diseases likely reflects shared pathogenic factors between different diseases. Familial aggregation of autoimmunity has not been examined in juvenile dermatomyositis. Interferon-α is thought to be a pathogenic factor in both systemic lupus erythematosus and juvenile dermatomyositis, and we have previously demonstrated familial aggregation of serum interferon-α.
  
  
  METHODS
  Family histories were obtained from 304 families of children with juvenile dermatomyositis via 3-generation structured interviews performed by the same person. Rates of autoimmune disease in families of children with juvenile dermatomyositis were compared with published population rates. Serum interferon-α, tumor necrosis factor-α, and neopterin were measured using standard techniques.
  
  
  RESULTS
  A total of 51% of families of children with juvenile dermatomyositis reported at least 1 additional member affected by an autoimmune disease. In particular, both type 1 diabetes and systemic lupus erythematosus were significantly more common than would be expected (odds ratio >5, P ≤ 1 × 10(-7) for both). Pedigree analysis showed particularly strong familial clustering of systemic lupus erythematosus with little decrease in incidence across generations, suggesting the possibility of rare causal genes with large effect. Untreated subjects with juvenile dermatomyositis with a family history of systemic lupus erythematosus had higher serum interferon-α than those who did not (P = .047).
  
  
  CONCLUSIONS
  We find strong familial aggregation of specific autoimmune diseases in families of children with juvenile dermatomyositis, suggesting that these conditions share pathogenic factors. Higher serum interferon-α in juvenile dermatomyositis patients with a family history of systemic lupus erythematosus suggesting that interferon-α is one such shared factor.
authors.affiliation: University of Chicago, Section of Rheumatology, Gwen Knapp Center for Lupus and Immunology Research, 924 E 57th St, R420, Chicago, IL 60637, USA. tniewold@medicine.bsd.uchicago.edu
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Niewold
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Wu
authors.forename: Molly
authors.initials: M
authors.lastname: Smith
authors.forename: Gabrielle A
authors.initials: GA
authors.lastname: Morgan
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Pachman
mesh_terms: D000293:Adolescent; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D016000:Cluster Analysis; D016208:Databases, Factual; D003882:Dermatomyositis / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D004198:Disease Susceptibility / Q000453:epidemiology*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D015994:Incidence; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D008297:Male; D010375:Pedigree; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D005819:Genetic Markers; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha