Cytosolic 5′-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis

Abstract

ObjectivesAutoantibodies directed against cytosolic 5′-nucleotidase 1A have been identified in many patients with inclusion body myositis. This retrospective study investigated the association between anticytosolic 5′-nucleotidase 1A antibody status and clinical, serological and histopathological features to explore the utility of this antibody to identify inclusion body myositis subgroups and to predict prognosis.Materials and methodsData from various European inclusion body myositis registries were pooled. Anticytosolic 5′-nucleotidase 1A status was determined by an established ELISA technique. Cases were stratified according to antibody status and comparisons made. Survival and mobility aid requirement analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression.ResultsData from 311 patients were available for analysis; 102 (33%) had anticytosolic 5′-nucleotidase 1A antibodies. Antibody-positive patients had a higher adjusted mortality risk (HR 1.89, 95% CI 1.11 to 3.21, p=0.019), lower frequency of proximal upper limb weakness at disease onset (8% vs 23%, adjusted OR 0.29, 95% CI 0.12 to 0.68, p=0.005) and an increased prevalence of excess of cytochrome oxidase deficient fibres on muscle biopsy analysis (87% vs 72%, adjusted OR 2.80, 95% CI 1.17 to 6.66, p=0.020), compared with antibody-negative patients.InterpretationDifferences were observed in clinical and histopathological features between anticytosolic 5′-nucleotidase 1A antibody positive and negative patients with inclusion body myositis, and antibody-positive patients had a higher adjusted mortality risk. Stratification of inclusion body myositis by anticytosolic 5′-nucleotidase 1A antibody status may be useful, potentially highlighting a distinct inclusion body myositis subtype with a more severe phenotype.

Anti‐NT5C1A autoantibodies for the diagnosis and study of the pathogenesis of sporadic inclusion body myositis

“…In our investigation, the percentage of patients with hepatitis C virus antibodies was significantly lower, and the mean area of type 2 myofibers was significantly smaller in the anti‐cN1A‐positive group compared with the autoantibody‐negative group . A recent retrospective study of 311 sIBM patients showed that the anti‐cN1A‐positive patients had a higher adjusted mortality risk, lower frequency of proximal upper limb weakness at disease onset and an increased prevalence of excess cytochrome oxidase‐deficient myofibers in muscle biopsy samples . Thus, the observation that patients with anti‐cN1A autoantibodies manifested distinct clinicopathological features might indicate the existence of a unique pathomechanism in sIBM.…”

Immune and myodegenerative pathomechanisms in inclusion body myositis

“…Two recent reports also found anti‐cN1A antibodies in 33% (102/311)143 and 35.8% (24/67)144 of IBM patients, respectively. The anti‐cN1A positive IBM patients showed a higher adjusted mortality risk and depicted more cytochrome oxidase deficient muscle fibers as compared to sero‐negative patients 143. Moreover, passive immunization with purified IgG fractions derived from either anti‐cN1A‐positive or anti‐cN1A‐negative IBM patients in in vitro and in vivo models, led to myodegenerative changes (such as p62 protein aggregation), resembling those observed in IBM muscle 144.…”

“…The presence of anti‐cN1A antibodies is neither associated with gender nor malignancy and appears to be independent of specific HLA‐DR alleles 141. Two recent reports also found anti‐cN1A antibodies in 33% (102/311)143 and 35.8% (24/67)144 of IBM patients, respectively. The anti‐cN1A positive IBM patients showed a higher adjusted mortality risk and depicted more cytochrome oxidase deficient muscle fibers as compared to sero‐negative patients 143.…”

Challenges in diagnosis and treatment of sporadic inclusion-body myositis

“…29−32 Probably, this antibody could be connected with a more severe phenotype and a higher adjusted mortality risk. 33 Treatment of sIBM still remains a major challenge due to the coexistence of autoinflammatory and degenerative processes. So far, there has not been enough evidence in favor of using glucocorticosteroids, methotrexate, cyclosporine, azathioprine, mycophenolate mofetil, or intravenous immunoglobulin.…”