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Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis.
Front Immunol 2019; 10:745FI

Abstract

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.

Authors+Show Affiliations

Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.Department of Pediatrics, McMaster University Medical Center, Hamilton, ON, Canada.Department of Pediatrics, McMaster University Medical Center, Hamilton, ON, Canada.Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.Hospital General de Occidente and University of Guadalajara, Guadalajara, Mexico. PANLAR Myositis Study Group, Guadalajara, Mexico.Inova Diagnostics, San Diego, CA, United States.Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31024569

Citation

Amlani, Adam, et al. "Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis." Frontiers in Immunology, vol. 10, 2019, p. 745.
Amlani A, Choi MY, Tarnopolsky M, et al. Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis. Front Immunol. 2019;10:745.
Amlani, A., Choi, M. Y., Tarnopolsky, M., Brady, L., Clarke, A. E., Garcia-De La Torre, I., ... Fritzler, M. J. (2019). Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis. Frontiers in Immunology, 10, p. 745. doi:10.3389/fimmu.2019.00745.
Amlani A, et al. Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis. Front Immunol. 2019;10:745. PubMed PMID: 31024569.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis. AU - Amlani,Adam, AU - Choi,May Y, AU - Tarnopolsky,Mark, AU - Brady,Lauren, AU - Clarke,Ann E, AU - Garcia-De La Torre,Ignacio, AU - Mahler,Michael, AU - Schmeling,Heinrike, AU - Barber,Claire E, AU - Jung,Michelle, AU - Fritzler,Marvin J, Y1 - 2019/04/09/ PY - 2018/09/22/received PY - 2019/03/19/accepted PY - 2019/4/27/entrez PY - 2019/4/27/pubmed PY - 2019/4/27/medline KW - Mup44 KW - anti-NT5c1A KW - autoantibodies KW - cytosolic 5-nucleotidase 1A KW - inclusion body myositis SP - 745 EP - 745 JF - Frontiers in immunology JO - Front Immunol VL - 10 N2 - 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. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/31024569/Anti-NT5c1A_Autoantibodies_as_Biomarkers_in_Inclusion_Body_Myositis L2 - https://doi.org/10.3389/fimmu.2019.00745 DB - PRIME DP - Unbound Medicine ER -