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.

FIGURE 1

Serum IFN-α activity in JDM patients stratified by family history of SLE and medical treatment status. Dots indicate individual JDM patients, and each dot is a unique patient. Lines show the median, error bars show the interquartile range, and P values are calculated using the Mann-Whitney U test.

FIGURE 2

Diagram showing familial associations with JDM in the context of previously reported familial autoimmune disease associations. Conditions that are increased in family members are indicated by connecting lines with arrowheads, whereas conditions that are decreased in relatives are indicated by connecting lines. T1DM indicates type 1 diabetes; CEL, celiac disease; IBD, inflammatory bowel disease; RA, rheumatoid arthritis; PSOR, psoriasis. The 4 lines originating from the JDM box represent the 4 significant associations described in this study, and other connectors represent previously reported associations in published literature.^–