Myositis-specific Autoantibodies and Their Clinical Significance

The role of myositis specific Antigens. (Suzuki. Nov. 2011) [1]

Dermatomyositis (DM) and polymyositis (PM) leads to progressive muscle weakness, skin disease as well as involvement of internal organs and cancer in adults. The conditions are characterized by histological features such as muscle cell infiltrations and specific alteration of the muscle fibers. Recent studies also strongly suggest involvement of myositis specific autoantibody (MSAs) in the etiology of the disease.

The above cited article elucidates the correlation between histological findings and myositis specific autoantibodies in the clinical phenotypes of DM and PM. In a study involving 207 patients with idiopathic inflammatory myopathies, MSAs were identified in 48% of the patients. The MSAs identified in these patients includes anti-signal recognition particle (SRP), anti-aminoacyl transfer RNA synthetase (ARS), anti-Ku, anti-U1RNP, and anti-SSA/B.

Further studies revealed that the anti-SRP antibodies are associated with sever weakness, muscle atrophy, elevated creatine kinase necrosis in muscle fibers, suggesting that these antibodies are the most relevant markers associated with both clinical and histological features of inflammatory myopathies. Anti-ARS antibodies, on the other hand, are associated with extramuscular symptoms and elevated C reactive protein. Anti-Ku and anti-U1RNP antibodies are found to be associated with rheumatic diseases.

These findings and further studies in this line will help in better understanding of the pathophysiology of idiopathic inflammatory myopathies as well as help to develop more effective therapy.  

Myositis Specific Antibodies

Myositis specific antibodies have a controversial pathogenic role. They may occasionally define the clinical phenotype, and offer a prognosis for a subset of patients; most are predictors of poor treatment response (53–56).

The MSA include: (1) Cytoplasmic antibodies directed against Mi-2 and Mas antigens. (2) Antibodies targeting translational proteins such as tRNA synthetases, anti (SRP), transcriptional intermediary factor-1 gamma (TIF-1; anti-155/140 Ab), and the melanoma differentiation-associated gene-5 (MDA5; anti-CADM140 Ab).

Jo-1 autoantibody is the most common tRNA synthetase antibody (up to 20% of IIM). The other antisynthetases (PL-7, PL-12, EJ, KS, OJ, Ha, and Zo) occur in <5% of IIM (57, 58). They all lead to a similar phenotype with ILD, arthritis, Raynaud’s phenomenon, and mechanics hands (59).

Antibody to nuclear matrix protein NXP2 (or MJ antibody) is one of the most common MSA in JDM, but occur in <2% of adult DM cases with up to 50% having an associated malignancy.

The anti-155/140 autoantibodies target TIF-1 and are strongly associated with malignancy in adults (89% specificity) (60, 61). However, in JDM patients, they are associated with calcinosis rather than cancer (62).

The anti-MDA5 antibodies mostly described in Asians is associated with amyopathic DM and aggressive ILD (63).

Antibodies to Mi-2, a 240-kDa nuclear helicase, are found in 15–30% of DM patients and associated with a favorable prognosis (64, 65) and suggestions of environmental trigger in adult DM (66).

The anti-SRP antibodies are associated with NAM or maybe non-specifically positive (67). Patients present with acute and severe proximal weakness, dilated cardiomyopathy, ILD, and are often steroid resistant (68).

Anti 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) antibodies (200/100 autoantibodies) have been described in patients with NAM and statin use (69). [2]

 

2.Malik A, Hyatt G, Idiopathic Inflammatory Myopathies: Clinical Approach and Management, Front Neurol. 2016; 7: 64., as found at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873503/

Footnotes:

1. Suzuki, Shigeaki , . Myositis-specific Autoantibodies and Their Clinical Significance. Brain and nerve = Shinkei kenkyū no shinpo, Volume: 63 ISSN: 1881-6096 , 2011 as found at VIEW