Expression of TNFα by muscle fibers in biopsies from children with untreated juvenile dermatomyositis:: Association with the TNFα-308A allele

Juvenile dermatomyositis (JDM) is the most common pediatric inflammatory myopathy. In patients with JDM, the A --> G polymorphism in the tumor necrosis factor alpha (TNF alpha)-308 promoter region (TNF alpha -308A) is associated with prolonged disease course and increased production of TNFa by peripheral blood mononuclear cells (Arthritis Rheum. 43, 2368-2377, 2000). Magnetic resonance imaging directed biopsies from 21 white children with untreated JDM were evaluated for TNF alpha expression. Using monoclonal antibody to TNF alpha, fresh frozen sections were processed by the standard immunohistochemical technique. We investigated the association among the expression of TNF alpha by muscle fibers, disease activity, duration of untreated disease, and the TNF alpha -308 polymorphism. Untreated children with JDM who had the TNF alpha -308A allele had an increased number of TNFa stained muscle fibers than children with the TNF alpha -308G allele (P = 0.001). There was no association with disease activity or duration of untreated disease. We speculate that muscle fiber production of TNFa provides a microenvironment in which TNF alpha acts synergistically with other mediators to prolong muscle fiber damage. (C) 2001 Academic Press.