Myositis associated anti-NT5C1A autoantibody in clinical practice

ABSTRACT Objective To define the diagnostic utility and clinicopathologic features correlating with anti-cytosolic 5′-nucleotidase 1A (NT5C1A) antibody positivity in idiopathic inflammatory myopathies (IIMs). Methods 4987 patients had anti-NT5C1A status clinically tested between 2014 and 2019 in the Washington University neuromuscular clinical laboratory. Using clinicopathologic information available for 630 of these patients, we classified them as inclusion body myositis (IBM), dermatomyositis, antisynthetase syndrome, immune-mediated necrotizing myopathy (IMNM), non-specific myositis, or non-inflammatory muscle diseases. Results Anti-NT5C1A was found in 182/287 patients with IBM (63%), 11/53 patients with dermatomyositis (21%), 7/27 patients with antisynthetase syndrome (26%), 9/76 patients with IMNM (12%), 20/84 patients with non-specific myositis (24%), and 6/103 patients with non-inflammatory muscle diseases (6%). The sensitivity and specificity of anti-NT5C1A seropositivity for the diagnosis of IBM was 63% and 85%, respectively. Anti-NT5C1A positive IBM patients had a higher frequency of finger flexion weakness ( p <0.01) and their biopsies harbored more COX negative fibers ( p =0.04). 18% of anti-NT5C1A negative IBM patients seroconverted to anti-NT5C1A positive on repeat testing. Conclusions This is the largest description of patients tested by a clinical diagnostic lab for anti-NT5C1A. We confirm the sensitivity and specificity of anti-NT5C1A for IBM and identified clinicopathologic features in IBM which correlate with anti-NT5C1A status. Notably, anti-NT5C1A testing increased both the diagnostic sensitivity and specificity of IBM when combined with patient age, gender and creatine kinase (CK) level. We propose that future IBM diagnostic criteria include anti-NT5C1A testing.