Autoantibodies to Cytosolic 5′-Nucleotidase 1A in Primary Sjögren’s Syndrome and Systemic Lupus Erythematosus

Abstract

IntroductionAutoantibodies to cytosolic 5′-nucleotidase 1A (cN-1A; NT5C1A) have a high specificity when differentiating sporadic inclusion body myositis from polymyositis and dermatomyositis. In primary Sjögren’s syndrome (pSS) and systemic lupus erythematosus (SLE) anti-cN-1A autoantibodies can be detected as well. However, various frequencies of anti-cN-1A reactivity have been reported in SLE and pSS, which may at least in part be explained by the different assays used. Here, we determined the occurrence of anti-cN-1A reactivity in a large number of patients with pSS and SLE using one standardized ELISA.MethodsSera from pSS (n = 193) and SLE patients (n = 252) were collected in five European centers. Anti-cN-1A, anti-Ro52, anti-nucleosome, and anti-dsDNA reactivities were tested by ELISA (Euroimmun AG) in a single laboratory. Correlations of anti-cN-1A reactivity with demographic data and clinical data (duration of disease at the moment of serum sampling, autoimmune comorbidity and presence of muscular symptoms) were analyzed using SPSS software.ResultsAnti-cN-1A autoantibodies were found on average in 12% of pSS patients, with varying frequencies among the different cohorts (range: 7–19%). In SLE patients, the anti-cN-1A positivity on average was 10% (range: 6–21%). No relationship was found between anti-cN-1A reactivity and the presence or absence of anti-Ro52, anti-nucleosome, and anti-dsDNA reactivity in both pSS and SLE. No relationship between anti-cN-1A reactivity and duration of disease at the moment of serum sampling and the duration of serum storage was observed. The frequency of muscular symptoms or viral infections did not differ between anti-cN-1A-positive and -negative patients. In both disease groups anti-cN-1A-positive patients suffered more often from other autoimmune diseases than the anti-cN-1A-negative patients (15 versus 5% (p = 0.05) in pSS and 50 versus 30% (p = 0.02) in SLE).ConclusionOur results confirm the relatively frequent occurrence of anti-cN-1A in pSS and SLE patients and the variation in anti-cN-1A reactivity between independent groups of these patients. The explanation for this variation remains elusive. The correlation between anti-cN-1A reactivity and polyautoimmunity should be evaluated in future studies. We conclude that anti-cN-1A should be classified as a myositis-associated-, not as a myositis-specific-autoantibody based on its frequent presence in SLE and pSS.

Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis

“…The clinical utility of anti-NT5c1A from a diagnostic, prognostic and treatment perspective in sIBM as previously reported is summarized in Table 1 and odds ratios (OR) with 95% confidence intervals (CIs) of six eligible studies (see section Methods and Supplemental Table 1) are displayed as a logarithmic forest plot in Figure 1. A wide range of sensitivities of anti-NT5c1A antibodies is reported in sIBM ranging from 33 to 80% and it has been suggested that anti-NT5c1A may not be as reliable a biomarker for sIBM as previously thought (8–12, 14). It is also unclear as to whether anti-NT5c1A antibodies are associated with a particular sIBM phenotype, such as increased disease severity, progression, mortality, or response to treatment (2, 8–10).…”

Inclusion‐body myositis and primary Sjögren syndrome: mechanisms for shared etiologies

“…Anti‐cN1A antibodies directed to a 43‐kd muscle‐specific autoantigen are a useful biomarker for sIBM, have high specificity in distinguishing sIBM from other subsets of inflammatory myopathies, and may have a role in pathogenesis. Importantly, however, they are not disease‐specific and have also been detected in patients with pSS …”

“…One study described 8 of 36 (22%) of patients with pSS and myalgia, who underwent muscle biopsy, showed histopathological features of IBM, although none had clinical features characteristic of this condition . The detection of anti‐cN1A, which is selectively associated with IBM rather than other forms of idiopathic inflammatory myopathies (IIM) in a substantial proportion (12%) of patients with pSS, suggests a specific predilection for sIBM among patients with pSS.…”

Prevalence of Novel Myositis Autoantibodies in a Large Cohort of Patients with Interstitial Lung Disease

“…Antibodies against cN1A were described in IBM, PM/DM, Ssc, SLE, and Sjögren's syndrome (range 0-37%). However, associations with ILD have not been identified [26,27,[30][31][32]43,45]. We demonstrated novel data regarding the presence of cN1A antibodies in ILDs, including ASS, HP, and IPF.…”

“…Here, we focus on relatively unknown antibodies, including antibodies specific for asparaginyl-t-RNA synthetase (anti-Ks), tyrosyl-t-RNA synthetase (anti-Ha), phenylanyl-t-RNA synthetase alpha (anti-Zoα), and cytosolic-5-nucleotidase-1A (anti-cN1A). Circulating antibodies specific for Ks, Ha, and cN1A have been described in inclusion body myositis (IBM), systemic sclerosis (Ssc), and Sjögren's syndrome, whereas anti-Zo has been identified in anti-synthetase syndrome (ASS) with ILD [26][27][28][29][30][31][32][33][34][35][36]. However, data are scarce on the prevalence and associations of these autoantibodies in CTD-ILD and other ILD.…”