Sequence homology between encephalomyocarditis virus protein VPI and histidyl-tRNA synthetase supports a hypothesis of molecular mimicry in polymyositis

Walker, E J; Jeffrey, Peter D.

doi:10.1016/0306-9877(88)90041-2

Cited by 44 publications

(13 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Viral infection has long been thought to be one of the potential etiologies for idiopathic inflammatory myopathies (29)(30)(31). Patients with C-ADM and/or rapidly progressive ILD usually experience an acute onset and a course that is resistant to immunosuppressive treatment; however, the recurrence rate is low if and when the patient recovers, suggesting a possible association between this disease subset and infection.…”

Section: Discussionmentioning

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

542

422

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

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

542

422

View full text Add to dashboard Cite

show abstract

“…[3][4][5][6] The patients with autoantibodies to the different aminoacyl-tRNA synthetases show similar clinical features, such as myositis, ILD, and arthritis, despite their different immunological specificities, suggesting that the immune response to molecules with analogous biological functions leads to a similar syndrome. [73][74][75] On the other hand, the finding that anti-PL-12 reacts with both alanyl-tRNA synthetase and tRNA Ala indicated an anti-idiotype hypothesis, which has not yet been defined. One hypothesis is that myogenic viruses interact with ARS, and the formation of viral RNA-ARS complexes or an alteration in the host proteins may lead to the formation of immunogenic complexes or to the induction of autoimmune responses.…”

Section: Pathogenic Mechanisms Of Autoantibodies In Myositismentioning

confidence: 99%

Humoral aspects of polymyositis/dermatomyositis

Hirakata

2000

Modern Rheumatology

View full text Add to dashboard Cite

Evidence of the involvement of systemic autoimmunity has been observed in polymyositis/dermatomyositis (PM/DM). Autoantibodies directed against various cellular constituents have been detected in most patients with PM/ DM, and about one-third of patients have autoantibodies (myositis-specific antibodies: MSAs) that are found specifically in myositis patients. These autoantibodies are closely associated with a characteristic clinical subgroup, and therefore help in establishing the correct diagnosis, classifying the myositis patients in a homogeneous subset, and facilitating the clinical and treatment follow-up. Autoantibodies to six of the aminoacyl tRNA synthetases are each associated with a similar syndrome marked by myositis, interstitial lung disease, arthritis, and other features constituting an "antisynthetase syndrome." Antibodies to other cytoplasmic antigens that are involved in protein synthesis or translation factors are seen in a small proportion of patients. Antisignal recognition particles are associated with severe, refractory myositis that differs significantly from antisynthetase syndrome. Antibodies to the nuclear antigen are specifically seen in patietnts with DM. Several autoantibodies, including anti-U1 RNP, anti-U2 RNP, anti-Ku, and anti-PM-Scl, have been associated with scleroderma-PM overlap. In recent years, these MSAs and their antigens have been characterized using molecular biology approaches. It is not known if the MSAs are involved in tissue injury or the pathogenesis of PM/DM. However, an understanding of the production mechanisms of these autoantibodies can provide insight into the etiology of this disorder.

show abstract

“…C'est surtout l'auto-antigène Jo-1 qui a été étudié permettant de discuter 5 mécanismes inducteurs. L'auto-antigène Jo-1 a une homologie de structure avec l'ARN du picornavirus, potentiellement responsable de myosites virales [77]. Cette théorie du mimétisme moléculaire, bien que séduisante, n'a pas été formellement confirmée.…”

Section: Le Rôle Inhibiteur Enzymatique Des Auto-anticorpsunclassified

Comment faire le diagnostic et mieux comprendre les myopathies inflammatoires ? L’utilité des auto-anticorps

et al. 2010

View full text Add to dashboard Cite

Sequence homology between encephalomyocarditis virus protein VPI and histidyl-tRNA synthetase supports a hypothesis of molecular mimicry in polymyositis

Cited by 44 publications

References 10 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

Humoral aspects of polymyositis/dermatomyositis

Comment faire le diagnostic et mieux comprendre les myopathies inflammatoires ? L’utilité des auto-anticorps

Contact Info

Product

Resources

About