A New Approach to the Classification of Idiopathic Inflammatory Myopathy

Love, Lori A.; Leff, Richard L.; Fraser, David; Targoff, Ira N.; Dalakas, Marinos C.; Plötz, Paul H.; Miller, Frederick W.

doi:10.1097/00005792-199111000-00002

Cited by 887 publications

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“…With the exception of the anti-Mas serum (Fig. 1, lane 17) from a patient with polymyositis and alcoholic rhabdomyolysis (29,30), RNA X was not immunoprecipitated by any of the control sera, nor was it seen using sera from patients with other hepatic diseases, nonhepatic autoimmune diseases, or from healthy donors.…”

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confidence: 92%

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Autoantibodies against a serine tRNA-protein complex implicated in cotranslational selenocysteine insertion.

Gelpí

Sontheimer

Rodríguez-Sánchez

1992

Proc. Natl. Acad. Sci. U.S.A.

142

114

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We describe an autoantibody specificity present in a subgroup of patients with a severe form of autoimmune chronic active hepatitis. These antibodies precipitate a 90-nucleotide RNA from human whole cell extracts and recognize a 48-kDa polypeptide in immunoblotting assays. The RNA is a UGA suppressor serine tRNA that carries selenocysteine (tRNAlserJs'¢), as shown by sequence analysis. The protein does not appear to be seryl-tRNA synthetase; rather, it is an excellent candidate for a factor involved in cotranslational selenocysteine incorporation in human cells.Autoantibodies reactive with cellular constituents are often detected in sera from patients with autoimmune disease. Autoantibodies that immunoprecipitate tRNA have been detected primarily in sera from patients with polymyositis (1-3) and, less frequently, in patients with systemic lupus erythematosus (4) and scleroderma (5). The reactive antigens are usually tRNA-associated proteins; in only a few cases are they the tRNAs themselves (4, 6). Some of these protein antigens have been identified as aminoacyl-tRNA synthetases (3, 6-10).Other well-characterized components of the protein synthetic machinery [for example, ribosomes (11), 5S ribonucleoprotein (12), and elongation factor la (13)] also act as autoantigens. One translational event, the incorporation of selenocysteine into a growing polypeptide chain, is not well-understood in eukaryotes, and to our knowledge, the factors involved in this process have not been implicated in autoimmunity. The synthesis of selenoproteins in Escherichia coli involves several reactions (for review, see ref. 14). Briefly, selenocysteine incorporation is cotranslational and requires an unusual suppressor aminoacyl-tRNA (selenocysteyl-tRNAsec, where Sec is selenocysteine) and a specific translation factor (the product of the selB gene) that substitutes for elongation factor Tu. Insertion is directed by certain UGA triplets that in other contexts act as termination codons. tRNASec is initially charged with serine to form seryltRNASec and is then converted to selenocysteyl-tRNAsec by the action of the selA (selenocysteine synthase) and selD gene products. In mammalian cells, selenocysteine incorporation also occurs at specific UGA codons, and a suppressor serine tRNA that carries selenocysteine (tRNA[Serlsec) has been detected (15). However, complete elucidation of the eukaryotic pathway (and identification of the factors involved) has not yet been achieved.Here we report that an RNA-protein complex is the target of an autoantibody specificity found in the sera of a subset of patients with autoimmune chronic active hepatitis (AI-CAH). The RNA corresponds to a previously identified human suppressor serine tRNA, and the antigenic protein may be a factor involved in the pathway of cotranslational incorporation of selenocysteine into specific polypeptide chains.MATERIALS AND METHODS Subjects. Sera from 35 patients with AI-CAH were collected over a period of 4 years at the Sant Pau and Valle Hebron Hospitals in Barcelona. ...

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confidence: 92%

“…2, lanes 1-7). Anti-Mas control serum (29,30) (Fig. 1, lane 7), did not detect a 48-kDa species (Fig.…”

mentioning

confidence: 92%

Autoantibodies against a serine tRNA-protein complex implicated in cotranslational selenocysteine insertion.

Gelpí

Sontheimer

Rodríguez-Sánchez

1992

Proc. Natl. Acad. Sci. U.S.A.

142

114

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“…The mean age at diagnosis is 42 years. At least 1 allele of HLA-DRw52 is seen in 91% of patients, and at least 1 DR3 allele is seen in 73% of patients (1)(2)(3)5). Clinically, patients with this syndrome have features of inflammatory myopathy, interstitial lung disease, arthritis, "mechanic's hands," Raynaud's phenomenon, and often, fever.…”

Section: Discussionmentioning

confidence: 99%

Idiopathic inflammatory myopathy of the antisynthetase (jo‐1) type associated with noncaseating granulomas

Moder

Gaffey

Matteson

1993

Arthritis & Rheumatism

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The idiopathic inflammatory myopathies are a heterogeneous group of syndromes that share the finding of chronic muscle inflammation. Recently, serologic subtyping of autoantibodies found in patients with these syndromes has been used to identify distinct clinical entities. We describe a 36-year-old woman who, based on the findings of polymyositis documented by both electromyography and muscle biopsy, features of Raynaud's phenomenon, symmetric polyarthritis, "mechanic's hands," and Jo-1 antibody positivity, was considered to have the antisynthetase subset of idiopathic inflammatory myopathy. In addition, the patient had granulomatous synovitis, and noncaseating granulomas were found in a breast nodule. This is the first published report of granuloma formation in the antisynthetase syndrome.The idiopathic inflammatory myopathies are a heterogeneous group of acquired syndromes that have the common feature of chronic muscle inflammation (1). Differences in autoantibodies present in patients with these syndromes appear to permit classification into subsets of disease that are more homogeneous with regard to clinical features, resporise to therapy, and prognosis (1-3) than was possible with the previous classification system (4). Herein we describe a

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“…Myositis-specific auto-antibodies have also been described and influence the phenotype of the inflammatory myopathy [1,3,12] . Antibodies directed against SRP and HMG-CoA reductase are characteristic of necrotizing myopathy.…”

Section: Discussionmentioning

confidence: 99%

Paraneoplastic necrotizing myopathy in association with metastatic malignant melanoma: two case reports and a review of the literature

Peterson

Buehring

Rush

et al. 2015

CRCP

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Necrotizing myopathy is a rare subtype of inflammatory myopathy characterized predominantly by muscle weakness without inflammation. While the association of malignancy and inflammatory myopathies such as dermatomyositis and polymyositis is well-recognized, necrotizing myopathy has rarely been reported in association with cancer and, to our knowledge, has not been previously reported in association with melanoma. We report two cases of necrotizing myopathy in association with metastatic malignant melanoma.

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A New Approach to the Classification of Idiopathic Inflammatory Myopathy

Cited by 887 publications

References 0 publications

Autoantibodies against a serine tRNA-protein complex implicated in cotranslational selenocysteine insertion.

Autoantibodies against a serine tRNA-protein complex implicated in cotranslational selenocysteine insertion.

Idiopathic inflammatory myopathy of the antisynthetase (jo‐1) type associated with noncaseating granulomas

Paraneoplastic necrotizing myopathy in association with metastatic malignant melanoma: two case reports and a review of the literature

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