RISK FACTORS

PATHOPHYSIOLOGY

REMEDIAL STEPS

  1. Home
  2. Anti-MDA5

Anti-MDA5

Anti-MDA5 antibody

Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease characterised by skin and muscle inflammation, internal organ involvement and serum disease-specific autoantibodies. The recently identified anti-MDA5 (melanoma differentiation-associated gene 5) antibodies are associated with clinically amyopathic DM (CADM), rapidly progressive interstitial lung disease, severe skin manifestations, and poor prognosis.(1)

Autoantibodies directed against the cytosolic pathogen sensor MDA5 (CADM 140) can mark this subtype of dermatomyositis which has been reported to associate, in particular ethnic groups, with severe progressive interstitial lung disease, poor prognosis and an hyperferritinemic status resembling hemophagocytic-like syndromes. MDA5 may be relevant in that Interferon-signature claimed to characterize inflammatory myopathies and dermatomyosits itself, but its role is not clear. As a fact, European patients with circulating anti-MDA5 autoantibodies may be clinically inhomogeneous and exhibit different rates of severity. (2)

The presence of anti-MDA5 Ab identifies the characteristic skin, musculoskeletal, pulmonary and prognostic features in patients with autoimmune diseases. In addition, anti-MDA5 Ab seems to predict a group of patients with CADM-complicated fatal RPILD. (3)

Clinical evidence

The investigators at Johns Hopkins found anti–MDA-5 antibodies in 11 of 160 patients, whereas the Chinese investigators found such antibodies in 26 of 64 patients. The U.S. patients were more likely to have mechanic's hands, polyarthropathy mimicking rheumatoid arthritis, and ILD, although not rapidly progressive ILD. The U.S. researchers noted no correlation of disease activity with titer of the antibody. The Chinese researchers also observed a correlation with ILD; in their patients, there was a correlation with rapidly progressive ILD. The antibody was not detected in any Chinese patients with polymyositis; therefore, when the analysis was restricted to patients with dermatomyositis or amyopathic dermatomyositis, the prevalence of MDA-5 antibodies was 26 of 43 Chinese patients. (4)


 

Relevance

Detection of anti-MDA5 antibody is a valuable tool for identifying DM patients with a high risk for developing RP-ILD, but the distribution of classic DM and CADM in patients with this antibody varies among ethnic groups. (5)

the autoantibodies found in patients with inflammatory myopathies have been mainly classified into several types by immunoprecipitation assays: anti-aminoacyl-tRNA synthetase antibodies (anti-ARS Abs), Abs to the signal recognition particle (anti-SRP Abs), anti-Mi2 Abs, PM/Scl-100 Abs and PM/Scl-75 polypeptides Abs (anti-PM-Scl Abs), anti-clinically amyopathic DM 140 kDa polypeptide Abs (anti-CADM-140 Abs), anti-155/140 kDa polypeptide Abs (anti-p155/140 Abs) and autoantibodies to a 142 kDa protein (anti-MJ Abs). These autoantibodies are strongly associated with the clinical presentation (6)

Further studies in larger cohorts are necessary to define the clinical significance of anti-MDA5 antibodies in PM and the use of this biomarker as a prognosis item on autoimmune diseases.


 

Footnotes

  1. Ceribelli A.Prevalence and clinical significance of anti-MDA5 antibodies in European patients with polymyositis/dermatomyositis. Clin Exp Rheumatol. 2014 Nov-Dec;32(6):891-7. Epub 2014 Aug 15.http://www.ncbi.nlm.nih.gov/pubmed/25151986

  2. Parronchi P.MDA5-positive dermatomyositis: an uncommon entity in Europe with variable clinical presentations. Clin Mol Allergy. 2015 Nov 9;13:22. doi: 10.1186/s12948-015-0031-y. eCollection 2015. http://www.ncbi.nlm.nih.gov/pubmed/26557046

  3. Koga T.The diagnostic utility of anti-melanoma differentiation-associated gene 5 antibody testing for predicting the prognosis of Japanese patients with DM. Rheumatology (Oxford). 2012 Jul;51(7):1278-84. doi: 10.1093/rheumatology/ker518. Epub 2012 Feb .http://www.ncbi.nlm.nih.gov/pubmed/22378718

  4. Hall JC et al. Anti–melanoma differentiation–associated protein 5–associated dermatomyositis: Expanding the clinical spectrum. Arthritis Care Res (Hoboken) 2013 Aug; 65:1307. (http://dx.doi.org/10.1002/acr.21992)

 

  1. Chen Z. Utility of anti-melanoma differentiation-associated gene 5 antibody measurement in identifying patients with dermatomyositis and a high risk for developing rapidly progressive interstitial lung disease: a review of the literature and a meta-analysis. Arthritis Care Res (Hoboken). 2013 Aug;65(8):1316-24. doi: 10.1002/acr.21985. http://www.ncbi.nlm.nih.gov/pubmed/23908005


 

  1. Sato S, . Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum 2005;52:1571-6. CrossRef

 

 


 










loading...