Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients

Abstract

Objectives To determine prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of idiopathic inflammatory myopathy (IIM) patients. Methods Adult patients with confirmed IIM recruited to the EuroMyositis registry (n = 1637) from four centres were investigated for the presence of MSAs/MAAs by radiolabelled-immunoprecipitation, with confirmation of anti -MDA5 and anti -NXP2 by ELISA. Clinical associations for each autoantibody were calculated for 1483 patients with a single or no known autoantibody by global linear regression modelling. Results MSAs/MAAs were found in 61.5% of patients, with 84.7% of autoantibody positive patients having a sole specificity, and only three cases (0.2%) having more than one MSA. The most frequently detected autoantibody was anti -Jo-1 (18.7%), with a further 21 specificities each found in 0.2–7.9% of patients. Autoantibodies to Mi-2, SAE, TIF1, NXP2, MDA5, PMScl and the non-Jo-1 tRNA-synthetases were strongly associated (p < 0.001) with cutaneous involvement. Anti -TIF1 and anti -Mi-2 positive patients had an increased risk of malignancy (OR 4.67 and 2.50 respectively), and anti -SRP patients had a greater likelihood of cardiac involvement (OR 4.15). Interstitial lung disease was strongly associated with the anti -tRNA synthetases, anti -MDA5, and anti -U1RNP/Sm. Overlap disease was strongly associated with anti -PMScl, anti -Ku, anti -U1RNP/Sm and anti -Ro60. Absence of MSA/MAA was negatively associated with extra-muscular manifestations. Conclusions Myositis autoantibodies are present in the majority of patients with IIM and identify distinct clinical subsets. Furthermore, MSAs are nearly always mutually exclusive endorsing their credentials as valuable disease biomarkers.

Inflammatory Myopathy-Related Interstitial Lung Disease: From Pathophysiology to Treatment

“…The description of IMs has largely evolved over the past decades (6,7). Based on clinical, immunological and histological features, five groups can be distinguished to date (Figure 1): (i) overlap myositis, which is the most common (ii) dermatomyositis, which often associates a specific skin involvement, (iii) immune mediated necrotizing myopathy (iv) sporadic inclusion body myositis and (v) polymyositis (8)(9)(10)(11).…”

Idiopathische Inflammatorische Myopathien: Klinisches Spektrum und Diagnostik

“…Durch die Assoziation mit Myositis-spezifischen bzw. -assoziierten Antikörpern ist die weitere Untergliederung in homogene Subtypen möglich [11]. So zeigt eine DM mit einem klassischen Exanthem in sonnenexponierten Arealen und Mi-2-Antikörpern typischerweise ein gutes Ansprechen auf Therapie.…”

“…Eine Überschneidung mit einer rheumatoiden Arthritis mit anti-CCP-Antikörpern ist möglich. Die wichtigsten Antisynthetase-Autoantikörper (ASAs) sind anti-Jo-1, und anti-(Aminoacyl-tRNA-Synthetasen) PL7, PL12, EJ, OJ, KS, Zo, Ha [11]. In Muskelbiopsien wurden als relativ spezifischer Befund perifaszikuläre Muskelfasernekrosen und eine Destruktion des perimysialen Bindegewebes beschrieben [15].…”

Microbial and autoantibody immunogenic repertoires in TIF1γ autoantibody positive dermatomyositis

“…These myositis-specific autoantibodies are often associated with particular clinical features. Individuals with autoantibodies targeting the cytoplasmic nucleic acid sensor MDA5 (also called interferon induced with helicase C domain 1, IFIH1) can present with rapidly progressive interstitial lung disease which is associated with high mortality (Abe et al, 2017;Betteridge et al, 2019). Several members of the tripartite motif (TRIM) protein family are known autoantibody targets in IIM, and there is a strong temporal association between adult-onset dermatomyositis and malignancy onset in individuals with antibodies to transcription intermediary factor 1γ (TIF1γ, TRIM33) (Oldroyd et al, 2019).…”