Autoantibodies to the p140 Autoantigen NXP-2 in Adult Dermatomyositis

Purpose: Myositis-specific autoantibodies (MSAs) define dermatomyositis (DM) and polymyositis (PM) into more homogeneous clinical subsets. Recently, anti-p140 has been demonstrated to form a major autoantibody subset in juvenile DM (JDM) [1-2]. The aim of this study was to investigate if autoantibodies to the same p140 autoantigen, nuclear matrix protein NXP-2, are present in adult myositis sera. Methods: Sera from 393 adults with myositis based on the Bohan and Peter diagnostic criteria recruited to Adult Onset Myositis Immunogenetic Collaboration (UK) and Institute of Rheumatology, Prague were autoantibody typed by immunoprecipitation using 35S-labelled K562 cells. Serum samples immunoprecipiating a 140-kd protein band were immunodepeleted with reference adult and JDM anti-p140 sera. Disease and normal control sera were screened using the above method. Clinical data was collated using standardised proformas. Probabilities were calculated using Fisher's exact test.Results: Sera from 11 (3%) of 393 patients with myositis were positive for anti-p140 autoantibodies, which were detected exclusively in 6% of DM. No anti-p140 antibody-positive patients were positive for other recognized autoantibodies. Immunodepletion using reference sera suggested that the identity of p140 was consistent with NXP-2. The major clinical features of anti-p140-positive patients were heliotrope rash (73%), Gottron’s lesions (82%), periungal erythema (91%) and systemic involvement including weight loss or fever (78%). In particular, the frequency of interstitial lung disease (ILD) in anti-p140-positive DM patients was 64% in comparison to 28% in anti-p140-negative DM patients (p=0.018), and 30% in anti-p140-negative group overall (p=0.04). There was no cancer-associated myositis in the adult anti-p140 positive subset. In contrast to anti-p140-positive JDM patients where calcinosis is a significant feature, this was only present in one patient (9%). Conclusions: Anti-p140 autoantibodies form a further serological subset in adult DM, although the frequency of this MSA is much lower than observed in JDM [1]. In addition, our preliminary data suggests that the clinical associations of anti-p140 autoantibodies in adults differ from JDM. In particular, ILD appears to be a major feature of anti-p140-positive adult DM associated with hallmark cutaneous disease.References: [1] Gunawardena et al, Arthritis Rheum 2009 60(6): 1807-14, [2] Targoff et al, Arthritis Rheum 2007 56:S787