Calcinosis in juvenile dermatomyositis is influenced by both anti-NXP2 autoantibody status and age at disease onset.

Sarah L Tansley,Gavin Shaddick,Lucy R Wedderburn,Katie Arnold,Zoe E Betteridge,Neil J Mchugh,Harsha Gunawardena

doi:10.1093/rheumatology/keu259

Abstract

Objective. Calcinosis is a major cause of morbidity in JDM and has previously been linked to anti-NXP2 autoantibodies, younger age at disease onset and more persistent disease activity. This study aimed to investigate the clinical associations of anti-NXP2 autoantibodies in patients with JDM stratified by age at disease onset.Methods. A total of 285 patients with samples and clinical data were recruited via the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-NXP2 was determined by both immunoprecipitation and ELISA. Logistic regression analysis was performed to assess the age-dependent relationship between anti-NXP2 and the development of calcinosis and disease activity measures.Results. We identified anti-NXP2 autoantibodies in 56 patients (20%). While in all patients younger age at disease onset was associated with an increased risk of calcinosis and this relationship was nearly linear, anti-NXP2 autoantibodies substantially increased the risk of calcinosis across all ages (P = 0.025) and were detectable prior to calcinosis development. Children with anti-NXP2 autoantibodies had a greater degree of weakness (median lowest ever Childhood Myositis Assessment Score 29.6 vs 42) and were less likely to be in remission at 2 years post-diagnosis. No difference in disease activity was seen 4 years post-diagnosis.Conclusion. Children diagnosed at a young age have a high risk of calcinosis regardless of autoantibody status. However, the presence of anti-NXP2 autoantibodies substantially increases the risk of calcinosis across all ages and is associated with disease severity.

Highlights

Our group has previously demonstrated that antibodies to a 140 kDa protein detected by protein immunoprecipitationSubmitted 18 November 2013; revised version accepted 2 May 2014.(known as anti-p140 or P140) in JDM were strongly associated with the development of calcinosis, a major cause of morbidity [1]
While in all patients younger age at disease onset was associated with an increased risk of calcinosis and this relationship was nearly linear, anti-NXP2 autoantibodies substantially increased the risk of calcinosis across all ages (P = 0.025) and were detectable prior to calcinosis development
Children with anti-NXP2 autoantibodies had a greater degree of weakness and were less likely to be in remission at 2 years post-diagnosis

Summary

Introduction

(known as anti-p140 or P140) in JDM were strongly associated with the development of calcinosis, a major cause of morbidity [1]. The presence of autoantibodies to a 142 kDa antigen (anti-MJ) in JDM has been shown by others to be associated with a severe disease course, worse functional status and persistent disease activity [2]. It is clear that the target of these autoantibodies is a 140 kDa protein, NXP2 (molecular weight 140 kDa). Anti-NXP2 autoantibodies are common in JDM and identifiable in 1323% of patients [1, 2]. JDM is a heterogeneous disease and autoantibodies are potentially useful biomarkers to divide patients into homogeneous subgroups and inform on prognosis. AntiNXP2 autoantibodies are of particular interest, given their

Methods

Results

Conclusion