Abstract

Idiopathic inflammatory myopathy (poly-dermatomyositis) is an inflammatory disease of muscle in which characteristic autoantibodies occur. By applying a broad range of immunological, clinical, and epidemiological observations to a large (expanded in the past year to over 250) group of patients, we have developed evidence for subsets of patients which strongly suggest that the disease can be divided into more meaningful groups with different etiology, pathogenesis and response to therapy. Studies on the seasonal and geographic distribution of disease sub-types are well underway. Laboratory studies have shown that the major autoantibody, anti-Jo-1, which defines a clinically important subgroup of patients, appears to be an antigen-driven secondary response directed to a conformational, not a linear, epitope of histidyl tRNA synthetase. The discovery of affinity-maturation in the early response to this antigen powerfully implicates the enzyme itself as the driving antigen.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Intramural Research (Z01)
Project #
1Z01AR041074-03
Application #
3810929
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  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
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
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
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

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