Laboratory testing in the diagnosis and management of idiopathic inflammatory myopathies

Targoff, Ira N.

doi:10.1016/s0889-857x(02)00032-7

Cited by 146 publications

(99 citation statements)

References 131 publications

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“…For example, anti-aaRS is associated with ILD, arthritis, Raynaud's phenomenon, and mechanic's hands (antisynthetase syndrome); anti-SRP is associated with severe refractory PM; anti-Mi-2 is associated with typical DM; and antip155 is associated with malignancy-associated DM. Therefore, these antibodies are useful in the diagnosis as well as classification of the disease (10).…”

mentioning

confidence: 99%

RNA helicase encoded by melanoma differentiation–associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease

Sato¹,

Hoshino²,

Satoh³

et al. 2009

Arthritis & Rheumatism

543

422

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ObjectiveTo identify the autoantigen recognized by the autoantibody that is associated with clinically amyopathic dermatomyositis (C‐ADM) and rapidly progressive interstitial lung disease (ILD).MethodsAn anti–CADM‐140 antibody–positive prototype serum sample was used to screen a HeLa cell–derived complementary DNA (cDNA) library. Selected cDNA clones were further evaluated by immunoprecipitation of their in vitro–transcribed and in vitro–translated products using anti–CADM‐140 antibody–positive and anti‐CADM‐140 antibody–negative sera. The lysates of COS‐7 cells transfected with the putative antigen were similarly tested. An enzyme‐linked immunosorbent assay (ELISA) to detect the anti–CADM‐140 antibody was established using a recombinant CADM‐140 antigen, and its specificity and sensitivity for C‐ADM and rapidly progressive ILD were assessed in 294 patients with various connective tissue diseases.ResultsBy cDNA library screening and immunoprecipitation of in vitro–transcribed and in vitro–translated products, we obtained a cDNA clone encoding melanoma differentiation–associated gene 5 (MDA‐5). The anti–CADM‐140 antibodies in patients' sera specifically reacted with MDA‐5 protein expressed in cells transfected with full‐length MDA‐5 cDNA, confirming the identity of MDA‐5 as the CADM‐140 autoantigen. The ELISA, using recombinant MDA‐5 protein as the antigen, showed an analytical sensitivity of 85% and analytical specificity of 100%, in comparison with the “gold standard” immunoprecipitation assay, and was useful for identifying patients with C‐ADM and/or rapidly progressive ILD.ConclusionGiven that RNA helicase encoded by MDA‐5 is a critical molecule involved in the innate immune defense against viruses, viral infection may play an important role in the pathogenesis of C‐ADM and rapidly progressive ILD. Moreover, our ELISA using recombinant MDA‐5 protein makes detection of the anti–CADM‐140 antibody routinely available.

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confidence: 99%

RNA helicase encoded by melanoma differentiation–associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease

Sato¹,

Hoshino²,

Satoh³

et al. 2009

Arthritis & Rheumatism

543

422

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“…There is a separate, immunologically and enzymatically distinct aminoacyl tRNA synthetase (ARS) in the cytoplasm for each of the 20 amino acids (1). Autoantibodies to six of the synthetases [Jo-1 (histidyl-tRNA synthetase: HisRS) (2, 3), PL-7 (threonyl-: ThrRS) (4), PL-12 (alanyl-: AlaRS) (5), OJ (isoleucyl-: IleRS) (6), EJ (glycyl-: GlyRS) (6), and KS (asparaginyl tRNA-: AsnRS) (7)] have been described in patients with connective tissue diseases, and these antibodies can be found in approximately 25-35% of patients with inflammatory muscle disorders, PM and DM (8)(9)(10).…”

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confidence: 99%

“…Anti-PL-7 (ThrRS) and anti-PL-12 (AlaRS) antibodies are less common, found in 3 to 4% of all patients with PM/DM, while autoantibodies to OJ (IleRS), EJ (GlyRS) and KS (AsnRS) are the least common, occurring in <2% (8)(9)(10).…”

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confidence: 99%

“…These autoantibodies are unique in having a combination of several important features: 1) they are directed at functionally related enzymes (performing the same function for different amino acids); 2) they are associated with a distinctive clinical syndrome; 3) they are mutually exclusive; individual patients have only a single anti-synthetase; and 4) strong immunogenetic associations have been described (10).…”

mentioning

confidence: 99%

“…Anti-ARSs have each been associated with a similar distinct syndrome referred to as "anti-synthetase syndrome" disease characterized by myositis with a high frequency of interstitial lung disease (ILD) and arthritis, as well as an increase when compared to the overall myositis population in Raynaud's phenomenon, fever with exacerbations, and "mechanic's hands (a hyperkeratosis with fissuring and hyperpigmentation along the radial and palmar aspects of the fingers resembling dirty horizontal lines associated with manual labor)" (8)(9)(10).…”

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confidence: 99%

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Autoantibodies to Aminoacyl-tRNA Synthetases

Hirakata

2005

Intern. Med.

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Anti–Melanoma Differentiation–Associated Protein 5–Associated Dermatomyositis: Expanding the Clinical Spectrum

Hall

Casciola‐Rosen

Samedy‐Bates

et al. 2013

Arthritis Care & Research

269

228

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Objective Autoantibodies against melanoma differentiation-associated protein 5 (MDA5) have been described in several Asian dermatomyositis (DM) cohorts, often associated with amyopathic DM and rapidly progressive interstitial lung disease (ILD). A recent study of a DM cohort seen at a US dermatology clinic reports that MDA5 autoantibodies are associated with a unique cutaneous phenotype. Given the widening spectrum of clinical findings, we evaluated the clinical features of anti-MDA5-positive patients seen at a US myositis referral center. Methods 160 DM patients were screened for MDA5 autoantibodies by immunoprecipitation and antibody titers were analyzed in longitudinal serum samples. Anti-MDA5 positive patients were evaluated for the presence of additional myositis autoantibodies. Patient clinical characteristics were compared by retrospective chart review. Results MDA5 was targeted in 11/160 (6.9%) patients with DM. Of these, nine presented with a symmetric polyarthropathy, six demonstrated overt clinical myopathy and eight had ILD. Eight anti-MDA5-positive patients exhibited the clinical attributes of the antisynthetase syndrome in the absence of Jo-1 or other anti-synthetase autoantibodies. MDA5 autoantibody titers did not correlate with clinical course. Conclusions MDA5 autoantibodies are found in DM patients presenting with a symmetric polyarthritis, clinically similar to rheumatoid arthritis. These patients often have features of the antisynthetase syndrome, but in the absence of antisynthetase autoantibodies. Most anti-MDA5 positive patients had overt clinical myopathy and ILD. The latter, while occasionally severe, typically resolved with immunosuppressive therapy. In this cohort, the MDA5 phenotype is frequently a clinical mimic of the antisynthetase syndrome and is not associated with rapidly progressive ILD.

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Laboratory testing in the diagnosis and management of idiopathic inflammatory myopathies

Cited by 146 publications

References 131 publications

RNA helicase encoded by melanoma differentiation–associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease

RNA helicase encoded by melanoma differentiation–associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease

Autoantibodies to Aminoacyl-tRNA Synthetases

Anti–Melanoma Differentiation–Associated Protein 5–Associated Dermatomyositis: Expanding the Clinical Spectrum

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