Anti-aminoacyl-tRNA synthetase antibodies

In polymyositis, anti-aminoacyl-tRNA synthetase (ARS) antibodies are closely associated with several complications, However, the clinical significance of anti-ARS antibodies is not well established.(1)

A distinct clinical entity—antisynthetase syndrome—is characterized by the presence of anti-ARS antibodies, myositis, ILD, fever, arthritis, Raynaud’s phenomenon, and mechanic’s hands. The most common anti-ARS antibody is anti-Jo-1. More recently described anti-ARS antibodies might confer a phenotype that is distinct from that of anti-Jo-1-positive patients and is characterized by a lower incidence of myositis and a higher incidence of ILD. Among patients with antisynthetase syndrome-related ILD, the response to immunosuppressive medications is generally, but not universally, favorable.(2)

Clinical evidence

Autoantibodies are detectable in the sera of 50% of PM/DM patients and consist of myositis-associated and myositis-specific antibodies (MAAs and MSAs, respectively). The MAAs are not specific to PM/DM and are found in a variety of autoimmune diseases. The MSAs are divided into those directed at the following: components of a nucleosome remodeling complex (anti-Mi-2); a macromolecular complex involved in RNA degradation and processing (anti-PM/Scl); ribonucleoproteins involved in translational transport (anti-signal recognition particle, or anti-SRP); and ribonucleoproteins involved in protein synthesis (anti-aminoacyl-tRNA synthetase antibodies, also known as antisynthetase antibodies, or anti-ARS).(3)

A specific subset of PM/DM patients have a clinical syndrome consisting of the presence of anti-ARS antibodies, ILD, and some of the following clinical features: fever, arthralgias, Raynaud’s phenomenon, and exanthema on the hands (also referred to as mechanic’s hands). This combination of findings is designated antisynthetase (AS) syndrome. (3)

Although MAAs are common, they are not universally seen in PM/DM patients; antinuclear antibodies (ANAs), anti-SSA/Ro antibodies, and anti-U1 ribonucleoprotein (anti-U1-RNP) antibodies are found in 52%, 12%, and 11%, respectively. In contrast, MSAs appear to define specific clinical phenotypes. Anti-Mi-2 antibodies are found in 4–14% of PM/DM patients and are associated with diffuse, cutaneous, steroid-sensitive skin involvement. (4)

Anti-Jo-1 was the first anti-ARS to be discovered and characterized. Perhaps because the other anti-ARS antibodies have only more recently been identified and few laboratories have the ability to test for them, anti-Jo-1 is the most commonly identified anti-ARS antibody, and most of the clinical data about AS syndrome is based on patients who are anti-Jo-1-positive. It is found in 20–30% of PM patients, in 5–10% of those with DM, and in 75% of all reported cases in which an anti-ARS is present.(5)

Relevance

The usual approach in several studies to therapy for PM-related ILD (including patients with AS syndrome) is to use a combination of glucocorticoids and a steroid-sparing agent (usually mycophenolate mofetil or azathioprine). They used cyclophosphamide for cases with clinically severe or rapidly progressive ILD. For patients in whom ILD worsens despite aggressive conventional therapy, rituximab has been used with moderate success, with the stabilization or improvement of 7 of the 11 patients evaluated in one case series . So this treatment could be part of a multifactorial protocol designment to improve the patient health. But it needs to be studied better and stablish these antibodies as PM biomarkers. (6)

 

Footnotes:

1. Hozumi H . Prognostic significance of anti-aminoacyl-tRNA synthetase antibodies in polymyositis/dermatomyositis-associated interstitial lung disease: a retrospective case control study. PLoS One. 2015 Mar 19;10(3):e0120313. doi: 10.1371/journal.pone.0120313. eCollection 2015. http://www.ncbi.nlm.nih.gov/pubmed/25789468.

2. Joshua S. Myositis-related interstitial lung disease and antisynthetase syndrome. J Bras Pneumol. Author manuscript; available in PMC 2013 Jun 9.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676869

3. Mahler M.the assay of choice for the detection of anti-PM/Scl autoantibodies? Autoimmun Rev. 2009;8(5):373–8. PubMed

4. Ghirardello A. Anti-Mi-2 antibodies. Autoimmunity. 2005;38(1):79–83. PubMed

5. Love LA. A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. Medicine (Baltimore) 1991;70(6):360–74. [PubMed]

6. Sem M. Rituximab treatment of the anti-synthetase syndrome: a retrospective case series. Rheumatology (Oxford) 2009;48(8):968–71. [PubMed]