ReviewThe clinical phenotype associated with myositis-specific and associated autoantibodies: A meta-analysis revisiting the so-called antisynthetase syndrome
Introduction
Idiopathic inflammatory myopathies (IIMs) comprise a group of acquired, heterogeneous, systemic diseases characterized by muscle involvement, elevated serum levels of muscle enzymes, electromyographic abnormalities, and inflammatory infiltrates in muscle biopsies [1], [2], [3]. According to their characteristic histopathologic features, IIMs can be classified as polymyositis (PM), dermatomyositis (DM), or inclusion body myositis (IBM) [1], [2]. IIMs are associated with numerous autoantibodies, present in around 50% of patients with PM or DM and directed towards defined nuclear and cytoplasmic antigens. Some of these autoantibodies, namely anti-SS-A, U1-RNP, and PM/Scl, are frequently detected in patients with other connective diseases associated with myositis, especially systemic sclerosis, and are referred to as myositis-associated autoantibodies (MAAs) or systemic sclerosis (SSc)-associated autoantibodies [4]. Other autoantibodies, recognizing a subset of aminoacyl-transfer RNA synthetases (ARS), SRP components, and nuclear helicase-ATPase Mi-2, are considered specific to IIMs (myositis-specific antibodies, MSAs) [2], [3]. Anti-ARS autoantibodies include anti-Jo1 (anti-histidyl), the most common, as well as anti-PL7 (anti-analyl), anti-PL12 (anti-threonyl), anti-OJ (anti-isoleucyl), anti-EJ (anti-glycyl), anti-KS (anti-asparaginyl), anti-SC (anti-lysyl), anti-JS (anti-glutaminyl), anti-Ha (or anti-YRS, anti-threonyl), anti-tryptophanyl, and anti-Zo (anti-phenylalanyl) autoantibodies [2], [3]. Several studies have shown an increased risk of interstitial lung disease (ILD) in patients with myositis who are positive for anti-ARS autoantibodies, compared to seronegative controls, an association often referred to as the so-called antisynthetase syndrome (ASS), encompassing arthritis, mechanic's hand [MH], fever, Raynaud's phenomenon [RPh], myositis and ILD [2], [5].
Several authors, including our group, have questioned the clinical delimitation and singularity of ASS. The definition of ASS was in fact based on a single, uncontrolled, historical series [5]. Comparisons with the clinical spectrum associated with other MSA or MAA are lacking or limited by a small sample size [6], [7], [8]. Moreover, the homogeneity of ASS is debated, several reports suggesting variable occurrences of particular symptoms according to the subtype of anti-ARS autoantibodies [9], [10]. Lastly, the clinical features described as being associated with anti-ARS autoantibodies largely overlap those of anti-PM/Scl-positive patients [11], [12]. The aim of this study is to provide an evidence-based description of the clinical characteristics of patients positive for anti-ARS and to compare these characteristics to those associated with other MSA and with MAA.
Section snippets
Methods
The methods used were in accordance with the recommendations of the Meta-analysis of Observational Studies in Epidemiology (MOOSE) Group [13].
Studies selected
A total of 702 studies were retrieved (Fig. 1). Both primary reviewers agreed on the inclusion of 27 studies [6], [7], [8], [9], [10], [15], [16], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39] encompassing 3487 patients (mean/median age range 41–50 years; males 24–38%) (Table 1). Anti-Jo1 autoantibodies were detected in 903 patients, non-anti-Jo1 ARS autoantibodies in 559 patients, anti-Mi2 in 154 patients, anti-SRP in 144
Discussion
This study is the first meta-analysis providing precise and controlled data on the delimitation of the clinical spectrum associated with anti-ARS autoantibodies. Our study distinguished two subgroups of patients: those positive for anti-ARS and presenting MSA with frequent general, pulmonary, articular and cutaneous involvement, and those manifesting fewer extramuscular signs and positive for anti-SRP and anti-Mi2 autoantibodies (with the exception of DM-specific rash in patients with anti-Mi2
Take-home messages
- •
Anti-aminoacyl-tRNA synthetase (ARS) autoantibodies delimit a heterogeneous subset of patients with a high prevalence of myositis, interstitial lung disease, arthralgia, Raynaud's phenomenon, fever, and mechanic's hand
- •
Mechanic's hand and also articular and muscular clinical signs were more frequently associated with anti-Jo1 autoantibodies, whereas interstitial lung disease and fever were significantly related to non-anti-Jo1 ARS autoantibodies.
- •
The populations delineated by anti-PM/Scl and
References (56)
- et al.
Polymyositis and dermatomyositis
Lancet
(2003) - et al.
Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review
Autoimmun Rev
(2014) - et al.
Myositis-specific and myositis-associated antibodies in overlap myositis in comparison to primary dermatopolymyositis: relevance for clinical classification: retrospective study of 169 patients
Joint Bone Spine
(2010) - et al.
Hierarchical cluster and survival analyses of antisynthetase syndrome: phenotype and outcome are correlated with anti-tRNA synthetase antibody specificity
Autoimmun Rev
(2012) - et al.
Meta-analysis in clinical trials
Control Clin Trials
(1986) - et al.
EasyMA: a program for the meta-analysis of clinical trials
Comput Methods Prog Biomed
(1997) - et al.
Antisynthetase syndrome: a retrospective study of 14 patients
Rev Med Interne
(2012) - et al.
Comparison of long-term outcome between anti-Jo1- and anti-PL7/PL12 positive patients with antisynthetase syndrome
Autoimmun Rev
(2012) - et al.
Number, characteristics, and classification of patients with dermatomyositis seen by dermatology and rheumatology departments at a large tertiary medical center
J Am Acad Dermatol
(2007) - et al.
Interstitial lung disease with autoantibodies against aminoacyl-tRNA synthetases in the absence of clinically apparent myositis
Semin Arthritis Rheum
(1996)