Anti-cN1A Autoantibody Seropositivity Is Associated with Increased Mortality Risk in Inclusion Body Myositis (I4.001)

OBJECTIVE To investigate the clinical utility of cytosolic 5’-nucleotidase 1A (cN1A/NT5c1A) autoantibody testing in Inclusion Body Myositis (IBM). BACKGROUND IBM pathogenesis is incompletely understood. Inflammatory and degenerative processes cause cumulative muscle damage. Recent identification of anti-cN1A/NT5c1A autoantibodies in ~1/3 of IBM patients offers insight into pathogenic mechanisms. The utility of classifying IBM patients by anti-cN1A serotype has not been thoroughly investigated. In diseases with pathogenic circulating autoantibodies, serotype can predict disease course, including treatment response. We investigated the potential for a similar role for anti-cN1A testing in IBM. METHODS Data from four European IBM registries (UK, Netherlands, France, Sweden) were pooled. Anti-cN1A serotyping by ELISA was performed as previously described. Cases were stratified by anti-cN1A serotype. For clinical characteristics, associations were investigated using logistic regression. For mortality and mobility-aid requirement analyses Kaplan-Meier curves were generated and Cox proportional hazards regression performed. RESULTS Data from 311 IBM patients were analysed, 102 (32.8[percnt]) were anti-cN1A seropositive. Mean age at onset did not differ according to serotype (61.6 years [SD=9.7] vs. 59.8 [SD=9.5], p=0.129). At onset, fewer seropositive patients had proximal arm weakness (8.3[percnt] vs. 23.2[percnt], OR 0.30, 95[percnt]CI=0.11-0.73, p=0.004). A higher proportion of seropositive patients had excess cytochrome oxidase deficient fibres on muscle biopsy (86.9[percnt] vs. 71.8[percnt], OR 2.61, 95[percnt]CI=1.08-6.97, p=0.022). During follow-up, 70 patients died at a mean age of 77.8 years (SD=8.2). Adjusted mortality risk was higher in the seropositive group (HR 1.95, 95[percnt]CI=1.17-3.27, p=0.011). The adjusted hazard ratio for mobility-aid requirement in the seropositive group was 1.42, (95[percnt]CI=0.99-2.04, p=0.056). CONCLUSIONS Anti-cN1A seropositivity was associated with an increased risk of mortality, suggesting a more severe disease phenotype. Further use of this serological method to interrogate IBM disease mechanisms are clearly required. Stratification of IBM by anti-cN1A serotype may prove important for future treatment decisions if disease modifying therapies for IBM become available. Disclosure: Dr. Lilleker has nothing to disclose. Dr. Rietveld (joint first author) has nothing to disclose. Dr. Badrising has received personal compensation for activities with Novartis as a speaker. Dr. Benveniste has received research support from Genzyme, Shire, CSL Behring, Novartis. Dr. Gheorghe has nothing to disclose. Dr. Hanna has received personal compensation for activities with Bristol-Myers Squibb as an employee. Dr. Herbert has nothing to disclose. Dr. Hilton-Jones has received personal compensation for activities with Novartis. Dr. Lamb has nothing to disclose. Dr. Lecky has nothing to disclose. Dr. Lundberg has received personal compensation for activities with Novartis. Dr. Machado has received personal compensation for activities with Novartis as a consultant. Dr. Mariampillai has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Parton has nothing to disclose. Dr. Peeters has nothing to disclose. Dr. Pye has nothing to disclose. Dr. Roberts has nothing to disclose. Dr. Sacconi has nothing to disclose. Dr. Saris has nothing to disclose. Dr. Cooper has nothing to disclose. Dr. Pruijn has received research support from NovioSMart. Dr. Chinoy has received research support from Roche and Novartis. Dr. van Engelen has received research support from Euroimmun.