Etiology and Pathogenesis of Idiopathic Inflammatory Myopathy in Humans

Plotz, P H.

Abstract

Idiopathic inflammatory myopathy (polymyositis, dermatomyositis, and related disorders) is a family of inflammatory diseases in which disease- specific autoantibodies occur and for which there is considerable indirect evidence pointing to a viral etiology. We have over the past several years, seen and studied and collected serum, blood, and muscle specimens from well over 450 patients suspected of having myositis. We have collected epidemiologic information on many patients. We have cloned, sequenced, and expressed histidyl-TRNA synthetase HRS, the principal target autoantigen in idiopathic polymyositis and dermatomyositis and are analyzing its structure and promoter. We have extended the analysis of HLA antigens in the sets of myositis patients defined by autoantibodies using the sequence specific oligonucleotide hybridization/PCR method. We have analyzed promoter activity of the HRS gene and are currently investigating translational control of its synthesis. We have successfully obtained high level expression of HRS, purified it, and crystallized it. A sensitive, specific, stable ELISA has been developed and a patent applied for. In collaboration with Dr. Terry O'Hanlan and Dr. Frederick Miller, we have analyzed T cell receptor usage in the muscle of some patients with myositis.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Type: Intramural Research (Z01)
• Project #: 1Z01AR041074-06
• Application #: 3770185
• Support Year: 6
• Fiscal Year: 1993

Institution

• Name: National Institute of Arthritis and Musculoskeletal and Skin Diseases
• Country: United States

Publications

Plotz, Paul H (2014) Autoimmunity: the history of an idea. Arthritis Rheumatol 66:2915-20

Harris-Love, M O; Shrader, J A; Koziol, D et al. (2009) Distribution and severity of weakness among patients with polymyositis, dermatomyositis and juvenile dermatomyositis. Rheumatology (Oxford) 48:134-9

Levine, Stuart M; Raben, Nina; Xie, Dan et al. (2007) Novel conformation of histidyl-transfer RNA synthetase in the lung: the target tissue in Jo-1 autoantibody-associated myositis. Arthritis Rheum 56:2729-39

Nagaraju, Kanneboyina; Rider, Lisa G; Fan, Chenguang et al. (2006) Endothelial cell activation and neovascularization are prominent in dermatomyositis. J Autoimmune Dis 3:2

Howard, O M Zack; Dong, Hui Fang; Su, Shao Bo et al. (2005) Autoantigens signal through chemokine receptors: uveitis antigens induce CXCR3- and CXCR5-expressing lymphocytes and immature dendritic cells to migrate. Blood 105:4207-14

Oppenheim, Joost J; Dong, Hui Fang; Plotz, Paul et al. (2005) Autoantigens act as tissue-specific chemoattractants. J Leukoc Biol 77:854-61

Nagaraju, Kanneboyina; Casciola-Rosen, Livia; Lundberg, Ingrid et al. (2005) Activation of the endoplasmic reticulum stress response in autoimmune myositis: potential role in muscle fiber damage and dysfunction. Arthritis Rheum 52:1824-35

Casciola-Rosen, Livia; Nagaraju, Kanneboyina; Plotz, Paul et al. (2005) Enhanced autoantigen expression in regenerating muscle cells in idiopathic inflammatory myopathy. J Exp Med 201:591-601

Plotz, Paul H (2003) The autoantibody repertoire: searching for order. Nat Rev Immunol 3:73-8

Howard, O M Zack; Dong, Hui Fang; Yang, De et al. (2002) Histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, autoantigens in myositis, activate chemokine receptors on T lymphocytes and immature dendritic cells. J Exp Med 196:781-91