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

Abstract Juvenile dermatomyositis (JDM) is the most common pediatric inflammatory myopathy. In patients with JDM, the A → G polymorphism in the tumor necrosis factor alpha (TNFα)-308 promoter region (TNFα-308A) is associated with prolonged disease course and increased production of TNFα 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 TNFα expression. Using monoclonal antibody to TNFα, fresh frozen sections were processed by the standard immunohistochemical technique. We investigated the association among the expression of TNFα by muscle fibers, disease activity, duration of untreated disease, and the TNFα-308 polymorphism. Untreated children with JDM who had the TNFα-308A allele had an increased number of TNFα stained muscle fibers than children with the TNFα-308G allele ( P = 0.001). There was no association with disease activity or duration of untreated disease. We speculate that muscle fiber production of TNFα provides a microenvironment in which TNFα acts synergistically with other mediators to prolong muscle fiber damage.

[1]  L. Pachman,et al.  TNFα-308A allele in juvenile dermatomyositis: Association with increased production of tumor necrosis factor α, disease duration, and pathologic calcifications , 2000 .

[2]  J. Boehm,et al.  Disease-modifying activity of SB 242235, a selective inhibitor of p38 mitogen-activated protein kinase, in rat adjuvant-induced arthritis. , 2000, Arthritis and rheumatism.

[3]  G. Hotamisligil,et al.  Mechanisms of TNF-alpha-induced insulin resistance. , 2009 .

[4]  W. Declercq,et al.  Immunolocalization of tumor necrosis factor-alpha and its receptors in inflammatory myopathies 1 This paper was presented at the 50th Annual Meeting of the American Academy of Neurology, Minneapolis, MN, USA, April 1998. 1 , 1999, Neuromuscular Disorders.

[5]  N. Sheibani.  Thrombospondin‐1, PECAM‐1, and Regulation of Angiogenesis , 2006, Histology and histopathology.

[6]  F. Miller,et al.  Classification and treatment of the juvenile idiopathic inflammatory myopathies. , 1997, Rheumatic diseases clinics of North America.

[7]  U. Andersson,et al.  Cytokine production in muscle tissue of patients with idiopathic inflammatory myopathies. , 1997, Arthritis and rheumatism.

[8]  H. Goebel,et al.  Cytokine Expression Profile in Idiopathic Inflammatory Myopathies , 1996, Journal of neuropathology and experimental neurology.

[9]  A. Reed,et al.  Association of the HLA-DQA1*0501 allele in multiple racial groups with juvenile dermatomyositis. , 1995, Human immunology.

[10]  R. Simsolo,et al.  The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. , 1995, The Journal of clinical investigation.

[11]  M. Wener,et al.  A broadened spectrum of juvenile myositis. Myositis-specific autoantibodies in children. , 1994, Arthritis and rheumatism.

[12]  C. Kennedy,et al.  Juvenile dermatomyositis associated with partial lipoatrophy. , 1993, Journal of the American Academy of Dermatology.

[13]  C. Ober,et al.  Molecular genetic studies of major histocompatibility complex genes in children with juvenile dermatomyositis: increased risk associated with HLA-DQA1 *0501. , 1991, Human immunology.

[14]  J. Friedman,et al.  Immunogenetic studies of juvenile dermatomyositis: HLA-DR antigen frequencies. , 1983, Arthritis and rheumatism.

[15]  A. Bohan,et al.  Polymyositis and dermatomyositis (second of two parts). , 1975 .