Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis
Objective: Sporadic Inclusion Body Myositis (sIBM) is an inflammatory myopathy (IIM) without a specific diagnostic biomarker until autoantibodies to the cytosolic 5′-nucleotidase 1A (NT5c1A/Mup44) were reported. The objectives of our study were to determine the sensitivity and specificity of anti-NT...
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doaj-2df5917891d5410a88d1e30317abe4b92020-11-24T21:19:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-04-011010.3389/fimmu.2019.00745426370Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body MyositisAdam Amlani0May Y. Choi1Mark Tarnopolsky2Lauren Brady3Ann E. Clarke4Ignacio Garcia-De La Torre5Ignacio Garcia-De La Torre6Michael Mahler7Heinrike Schmeling8Claire E. Barber9Michelle Jung10Marvin J. Fritzler11Cumming School of Medicine, University of Calgary, Calgary, AB, CanadaCumming School of Medicine, University of Calgary, Calgary, AB, CanadaDepartment of Pediatrics, McMaster University Medical Center, Hamilton, ON, CanadaDepartment of Pediatrics, McMaster University Medical Center, Hamilton, ON, CanadaCumming School of Medicine, University of Calgary, Calgary, AB, CanadaHospital General de Occidente and University of Guadalajara, Guadalajara, MexicoPANLAR Myositis Study Group, Guadalajara, MexicoInova Diagnostics, San Diego, CA, United StatesCumming School of Medicine, University of Calgary, Calgary, AB, CanadaCumming School of Medicine, University of Calgary, Calgary, AB, CanadaCumming School of Medicine, University of Calgary, Calgary, AB, CanadaCumming School of Medicine, University of Calgary, Calgary, AB, CanadaObjective: Sporadic Inclusion Body Myositis (sIBM) is an inflammatory myopathy (IIM) without a specific diagnostic biomarker until autoantibodies to the cytosolic 5′-nucleotidase 1A (NT5c1A/Mup44) were reported. The objectives of our study were to determine the sensitivity and specificity of anti-NT5c1A for sIBM, demonstrate demographic, clinical and serological predictors for anti-NT5c1A positivity and determine if anti-nuclear antibody (ANA) indirect immunofluorescence (IIF) staining on HEp-2 cells is a reliable screening method for anti-NT5c1A.Methods: Sera from sIBM patients and controls were stored at −80°C until required for analysis. IgG antibodies to NT5c1A were detected by an addressable laser bead immunoassay (ALBIA) using a full-length human recombinant protein. Autoantibodies to other autoimmune myopathy antigens (Jo-1, OJ, TIF1y, PL-12, SAE, EJ, MDA5, PL7, SRP, NXP2, MI-2) were detected by line immunoassay (LIA), chemiluminescence immunoassay (CIA) or enzyme linked immunosorbent assay (ELISA) and ANA detected by IIF on HEp-2 substrate. Demographic, clinical and serological data were obtained by chart review.Results: Forty-three patients with sIBM, 537 disease control patients with other autoimmune, degenerative and neuromuscular diseases, and 78 healthy controls were included. 48.8% (21/43) of sIBM patients were positive for anti-NT5c1A. The overall sensitivity, specificity, positive predictive value, and negative predictive value of anti-NT5c1A for sIBM were 0.49, 0.92, 0.29, and 0.96, respectively. Compared to sIBM, the frequency of anti-NT5c1A was lower in both the disease control group (8.8%, OR 0.10 [95%CI: 0.05–0.20], p < 0.0001) and in the apparently healthy control group (5.1%, OR 0.06 [95%CI: 0.02–0.18], p < 0.0001). In the univariable analysis, sIBM patients with more severe muscle weakness were more likely to be anti-NT5c1A positive (OR 4.10 [95% CI: 1.17, 14.33], p = 0.027), although this was not statistically significant (adjusted OR 4.30 [95% CI: 0.89, 20.76], p = 0.069) in the multivariable analysis. The ANA of sIBM sera did not demonstrate a consistent IIF pattern associated with anti-NT5c1A.Conclusions: Anti-NT5c1A has moderate sensitivity and high specificity for sIBM using ALBIA. The presence of anti-NT5c1A antibodies may be associated with muscle weakness. Anti-NT5c1A antibodies were not associated with a specific IIF staining pattern, hence screening using HEp-2 substrate is unlikely to be a useful predictor for presence of these autoantibodies.https://www.frontiersin.org/article/10.3389/fimmu.2019.00745/fullinclusion body myositisanti-NT5c1AMup44cytosolic 5-nucleotidase 1Aautoantibodies |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Adam Amlani May Y. Choi Mark Tarnopolsky Lauren Brady Ann E. Clarke Ignacio Garcia-De La Torre Ignacio Garcia-De La Torre Michael Mahler Heinrike Schmeling Claire E. Barber Michelle Jung Marvin J. Fritzler |
spellingShingle |
Adam Amlani May Y. Choi Mark Tarnopolsky Lauren Brady Ann E. Clarke Ignacio Garcia-De La Torre Ignacio Garcia-De La Torre Michael Mahler Heinrike Schmeling Claire E. Barber Michelle Jung Marvin J. Fritzler Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis Frontiers in Immunology inclusion body myositis anti-NT5c1A Mup44 cytosolic 5-nucleotidase 1A autoantibodies |
author_facet |
Adam Amlani May Y. Choi Mark Tarnopolsky Lauren Brady Ann E. Clarke Ignacio Garcia-De La Torre Ignacio Garcia-De La Torre Michael Mahler Heinrike Schmeling Claire E. Barber Michelle Jung Marvin J. Fritzler |
author_sort |
Adam Amlani |
title |
Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis |
title_short |
Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis |
title_full |
Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis |
title_fullStr |
Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis |
title_full_unstemmed |
Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis |
title_sort |
anti-nt5c1a autoantibodies as biomarkers in inclusion body myositis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-04-01 |
description |
Objective: Sporadic Inclusion Body Myositis (sIBM) is an inflammatory myopathy (IIM) without a specific diagnostic biomarker until autoantibodies to the cytosolic 5′-nucleotidase 1A (NT5c1A/Mup44) were reported. The objectives of our study were to determine the sensitivity and specificity of anti-NT5c1A for sIBM, demonstrate demographic, clinical and serological predictors for anti-NT5c1A positivity and determine if anti-nuclear antibody (ANA) indirect immunofluorescence (IIF) staining on HEp-2 cells is a reliable screening method for anti-NT5c1A.Methods: Sera from sIBM patients and controls were stored at −80°C until required for analysis. IgG antibodies to NT5c1A were detected by an addressable laser bead immunoassay (ALBIA) using a full-length human recombinant protein. Autoantibodies to other autoimmune myopathy antigens (Jo-1, OJ, TIF1y, PL-12, SAE, EJ, MDA5, PL7, SRP, NXP2, MI-2) were detected by line immunoassay (LIA), chemiluminescence immunoassay (CIA) or enzyme linked immunosorbent assay (ELISA) and ANA detected by IIF on HEp-2 substrate. Demographic, clinical and serological data were obtained by chart review.Results: Forty-three patients with sIBM, 537 disease control patients with other autoimmune, degenerative and neuromuscular diseases, and 78 healthy controls were included. 48.8% (21/43) of sIBM patients were positive for anti-NT5c1A. The overall sensitivity, specificity, positive predictive value, and negative predictive value of anti-NT5c1A for sIBM were 0.49, 0.92, 0.29, and 0.96, respectively. Compared to sIBM, the frequency of anti-NT5c1A was lower in both the disease control group (8.8%, OR 0.10 [95%CI: 0.05–0.20], p < 0.0001) and in the apparently healthy control group (5.1%, OR 0.06 [95%CI: 0.02–0.18], p < 0.0001). In the univariable analysis, sIBM patients with more severe muscle weakness were more likely to be anti-NT5c1A positive (OR 4.10 [95% CI: 1.17, 14.33], p = 0.027), although this was not statistically significant (adjusted OR 4.30 [95% CI: 0.89, 20.76], p = 0.069) in the multivariable analysis. The ANA of sIBM sera did not demonstrate a consistent IIF pattern associated with anti-NT5c1A.Conclusions: Anti-NT5c1A has moderate sensitivity and high specificity for sIBM using ALBIA. The presence of anti-NT5c1A antibodies may be associated with muscle weakness. Anti-NT5c1A antibodies were not associated with a specific IIF staining pattern, hence screening using HEp-2 substrate is unlikely to be a useful predictor for presence of these autoantibodies. |
topic |
inclusion body myositis anti-NT5c1A Mup44 cytosolic 5-nucleotidase 1A autoantibodies |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.00745/full |
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