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

Juvenile dermatomyositis (JDM) is the most common pediatric inflammatory my opathy. In patients with JDM, the A --> G polymorphism in the tumor necrosi s factor alpha (TNF alpha)-308 promoter region (TNF alpha -308A) is associa ted with prolonged disease course and increased production of TNFa by perip heral blood mononuclear cells (Arthritis Rheum. 43, 2368-2377, 2000). Magne tic resonance imaging directed biopsies from 21 white children with untreat ed JDM were evaluated for TNF alpha expression. Using monoclonal antibody t o TNF alpha, fresh frozen sections were processed by the standard immunohis tochemical technique. We investigated the association among the expression of TNF alpha by muscle fibers, disease activity, duration of untreated dise ase, and the TNF alpha -308 polymorphism. Untreated children with JDM who h ad the TNF alpha -308A allele had an increased number of TNFa stained muscl e fibers than children with the TNF alpha -308G allele (P = 0.001). There w as no association with disease activity or duration of untreated disease. W e speculate that muscle fiber production of TNFa provides a microenvironmen t in which TNF alpha acts synergistically with other mediators to prolong m uscle fiber damage. (C) 2001 Academic Press.