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Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis.

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.

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  • Authors+Show Affiliations

    ,

    Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

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    Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

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    Department of Pediatrics, McMaster University Medical Center, Hamilton, ON, Canada.

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    Department of Pediatrics, McMaster University Medical Center, Hamilton, ON, Canada.

    ,

    Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

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    Hospital General de Occidente and University of Guadalajara, Guadalajara, Mexico. PANLAR Myositis Study Group, Guadalajara, Mexico.

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    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.

    Source

    Frontiers in immunology 10: 2019 pg 745

    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://dx.doi.org/10.3389/fimmu.2019.00745 DB - PRIME DP - Unbound Medicine ER -