Overview

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)

MDA5 (Melanoma Differentiation-Associated protein 5) 
is a RIG-I-like receptor dsRNA helicase enzyme that in humans is encoded by the IFIH1 gene.MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2, and functions as a pattern recognition receptor (recognizing dsRNA) that is a sensor for viruses (2)

In PM/DM, complications are associated with anti-aminoacyl-tRNA synthetase (ARS), including Jo-1 antibody or anti-melanoma differentiation-associated gene 5 (MDA5) antibody [1,3]

So in this diagram we can see the interactions.

Several viruses and immune diseases encode proteins that directly interfere with MDA5 to decrease interferon production by infected cells. For example, all viruses from paramyxovirinae subfamily encode a protein V able to interact with MDA5 and block MDA5 interaction with MAVS, its downstream partner in the cascade. The interaction has been investigated in detail and the C-terminal domain of the V proteins is responsible for the binding of the helicase domain of protein V.(4)

Several studies confirms that anti-MDA5 antibodies are not uncommon. All anti-MDA5 (+) cases are affected by CADM with typical skin disease, while rapidly progressive pulmonary involvement was diagnosed only in one case. Further studies in larger cohorts are necessary to define the clinical significance of anti-MDA5 antibodies in European PM/DM. (3)

Autoantibodies against aminoacyl-tRNA synthetases (ARS) have been found to be highly specific for polymyositis and dermatomyositis (PM/DM). Autoantibodies against aminoacyl-tRNA synthetases (ARS), a group of cytoplasmic enzymes, have been found to be highly specific for polymyositis and dermatomyositis (PM/DM), and to strongly correlate with complicating interstitial pneumonia (IP). Eight anti-ARS autoantibodies have been identified. These include anti-Jo-1, anti-PL-7, anti-PL-12, anti-OJ, anti-EJ, anti-KS, anti-Zo, and anti-Ha. (4)

It was reported that patients with anti-ARS antibody-positive IP have common clinical and pathological features. In one study, 14 patients with anti-ARS antibodies were examined. They concluded their results indicated that patients usually have a good response to corticosteroid treatment, however some have a rapidly worsening course and recurrence, despite therapy. (5)

So the detection of antibodies is important for estimating the clinical course. Further researchs can lead us to understand this better.

Footnotes:

1. Mimori T.Interstitial lung disease in myositis: clinical subsets, biomarkers, and treatment. Curr Rheumatol Rep 2012;14:264-74CrossRefMedlineGoogle Scholar

2. Kato H. "Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5". J Exp Med. 205 (7): 1601–1610. doi:10.1084/jem.20080091. PMC 2442638. PMID 18591409.

3. Marie I. Morbidity and mortality in adult polymyositis and dermatomyositis. Curr Rheumatol Rep 2012;14:275-85.CrossRefMedlineGoogle Scholar

4. Mimori, I.Autoantibodies in idiopathic inflammatory myopathy: an update on clinical and pathophysiological significance.Curr Opin Rheumatol, 19 (6) (2007), pp. 523–529. Citing articles (73)

5.  Hirakata, S. Anti-KS: identification of autoantibodies to asparaginyl-transfer RNA synthetase associated with interstitial lung diseas. J Immunol, 162 (4) (1999), pp. 2315–2320.View Record in Scopus