Cytosolic 5′‐Nucleotidase 1A As a Target of Circulating Autoantibodies in Autoimmune Diseases

Abstract

Objective Prior investigations demonstrated that autoantibodies recognizing cytosolic 5′-nucleotidase 1A (NT5C1A) are found in 33–76% of patients with inclusion body myositis (IBM) but are observed only rarely in patients with polymyositis (PM). Thus, anti-NT5C1A may help distinguish IBM from PM. Although 4–21% of patients with dermatomyositis (DM) were shown to be anti-NT5C1A antibody positive, the clinical features of anti-NT5C1A–positive patients with DM have not been described. Furthermore, the prevalence of anti-NT5C1A antibodies in other rheumatic conditions has not been reported. This study was undertaken to define the prevalence and clinical features of anti-NT5C1A–positive patients with DM, PM, IBM, or other systemic autoimmune diseases. Methods We screened for anti-NT5C1A autoantibodies in patients with IBM, DM, PM, Sjögren’s syndrome (SS), or systemic lupus erythematosus (SLE) and in healthy volunteers. Clinical characteristics were compared between patients who were anti-NT5C1A positive and those who were anti-NT5C1A negative. Results Anti-NT5C1A autoantibodies were detected in 71 (61%) of 117 patients with IBM, 2 (5%) of 42 patients with PM, 2 (5%) of 42 healthy volunteers, 24 (15%) of 159 patients with DM, 10 (23%) of 44 patients with SS, and 13 (14%) of 96 patients with SLE. No anti-NT5C1A antibody–positive patients with SS or SLE had muscle involvement. Anti-NT5C1A–positive patients with IBM had a lower prevalence of rimmed vacuoles (62% versus 83% of antibody-negative patients; P = 0.02). No differences in the clinical characteristics of antibody-positive and antibody-negative patients with DM, SS, or SLE were observed. Conclusion Anti-NT5C1A is a common target of circulating autoantibodies, especially in IBM but also in several different autoimmune diseases. In SLE and SS, anti-NT5C1A autoreactivity is not associated with muscle disease.

BACE-1, PS-1 and sAPPβ Levels Are Increased in Plasma from Sporadic Inclusion Body Myositis Patients: Surrogate Biomarkers among Inflammatory Myopathies

“…Salajegheh et al reported the existence of circulating autoantibodies against a 43-kDa muscle protein called CN1A, highly specific to IBM (13,14), although recent investigations found this autoantibody in other autoimmune diseases (15). Apart from this report, there is no information about noninvasive circulating diagnostic biomarkers in sIBM.…”

Development and evaluation of a standardized ELISA for the determination of autoantibodies against cN-1A (Mup44, NT5C1A) in sporadic inclusion body myositis

“…In particular, the clinical distinction between sIBM and polymyositis can be challenging, the latter being the most common initial misdiagnosis. Recent studies have reported anti-cN-1A reactivity in the serum of 33–76% patients with sIBM, but in not more than 5% of patients with polymyositis, with an overall specificity varying between 87 and 100% depending on the methodology and cohorts studied [29–31, 36–39]. Thus, the determination of anti-cN-1A autoantibodies is useful for distinguishing sIBM from other inflammatory myopathies.…”

Immune and myodegenerative pathomechanisms in inclusion body myositis

“…Moderate reactivity of anti‐cN1A antibodies was reported to be 70% sensitive and 92% specific for the diagnosis of IBM 136. Another study reported similar numbers, detecting anti‐cN1A antibodies in 61% of IBM patients but on the other hand also in 5% of PM, 23% of Sjögren's syndrome patients (SS), and 14% of systemic lupus erythematosus (SLE) patients, even in absence of any muscular symptoms 140. In a subsequent report however, the frequency of seropositive IBM patients was only 34.8% (24/69) 141.…”