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

abstract: ...Purpose Sporadic inclusion body myositis (sIBM) is an autoimmune degenerative disease of the muscle, with inflammatory infiltrates and inclusion vacuoles. Its pathogenesis is not fully understood and the diagnosis is hampered by its imprecise characteristics, at times indistinguishable from other idiopathic inflammatory myopathies such as polymyositis and dermatomyositis. The diagnosis may be assisted by the detection of autoantibodies targeting Mup44, a skeletal muscle antigen identified as cytosolic 5-nucleotidase 1A (cN-1A, NT5C1A). A novel standardized anti-cN-1A IgG ELISA was developed and its diagnostic performance was evaluated by two reference laboratories. Methods Recombinant human full-length cN-1A was expressed and purified, and subsequently utilized to set up a standardized ELISA. To evaluate the novel assay, laboratory A examined sera from North American patients with clinically and pathologically diagnosed definite sIBM ( n =17), suspected sIBM ( n =14), myositis controls ( n =110), non-myositis autoimmune controls ( n =93) and healthy subjects ( n =52). Laboratory B analyzed a Dutch cohort of definite sIBM patients ( n =51) and healthy controls ( n =202). Results Anti-cN-1A reactivity was most frequent in definite sIBM (39.247.1%), but absent in biopsy-proven classic polymyositis or dermatomyositis. Overall diagnostic sensitivity and specificity amounted to 35.5 and 96.1% (laboratory A) and 39.2 and 96.5% (laboratory B). Conclusions Anti-cN-1A autoantibodies were detected by ELISA with moderate sensitivity, but high specificity for sIBM and may therefore help diagnose this infrequent and difficult-to-diagnose myopathy. The novel anti-cN-1A IgG ELISA can improve and accelerate the diagnosis of sIBM using sera where muscle biopsy is delayed or unfeasible.

...Auto Immun Highlights Auto Immun Highlights Auto-Immunity Highlights 2038-0305 2038-3274 Springer International Publishing Cham 27858337 5114199 88 10.1007/s13317-016-0088-8 Original Article Development and evaluation of a standardized ELISA for the determination of autoantibodies against cN-1A (Mup44, NT5C1A) in sporadic inclusion body myositis Kramp Sabine L. 1 Karayev Dmitry 2 Shen Guo 2 Metzger Allan L. 2 Morris Robert I. 2 Karayev Eugene 2 Lam Yvonne 2 Kazdan Richard M. 2 Pruijn Ger J. M. 3 Saschenbrecker Sandra 1 Dhnrich Cornelia 1 Schlumberger Wolfgang +49-451-5855-0 w.schlumberger@euroimmun.de 1 1 Institute for Experimental Immunology, Euroimmun AG, Seekamp 31, 23560 Lbeck, Germany 2 RDL Reference Laboratory Inc., 10755 Venice Blvd., Los Angeles, CA 90034 USA 3 Department of Biomolecular Chemistry, Institute for Molecules and Materials and Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands 17 11 2016 17 11 2016 12 2016 7 1 16 6 7 2016 25 10 2016 The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Purpose Sporadic inclusion body myositis (sIBM) is an autoimmune degenerative disease of the muscle, with inflammatory infiltrates and inclusion vacuoles. Its pathogenesis is not fully understood and the diagnosis is hampered by its imprecise characteristics, at times indistinguishable from other idiopathic inflammatory myopathies such as polymyositis and dermatomyositis. The diagnosis may be assisted by the detection of autoantibodies targeting Mup44, a skeletal muscle antigen identified as cytosolic 5-nucleotidase 1A (cN-1A, NT5C1A). A novel standardized anti-cN-1A IgG ELISA was developed and its diagnostic performance was evaluated by two reference laboratories. Methods Recombinant human full-length cN-1A was expressed and purified, and subsequently utilized to set up a standardized ELISA. To evaluate the novel assay, laboratory A examined sera from North American patients with clinically and pathologically diagnosed definite sIBM ( n =17), suspected sIBM ( n =14), myositis controls ( n =110), non-myositis autoimmune

...-Mup44 autoantibodies was identified as cytosolic 5-nucleotidase 1A (cN-1A, cN1A, NT5C1A, Mup44) [ 29 31 ], a 41kDa enzyme that is most abundant in the skeletal muscle, catalyzing nucleotide hydrolysis and regulating nucleotide metabolism [ 32 , 33 ]. In patients with sIBM, the aberrant accumulation of cN-1A in areas of myofiber degeneration may contribute to its antigenicity, providing a plausible link between myodegenerative and autoimmune features in disease pathogenesis [ 30 ]. Anti-cN-1A

...-nucleotidase autoantibodies in inclusion body myositis: isotypes and diagnostic utility Muscle Nerve 2014 50 488 492 10.1002/mus.24199 24752512 37. Goyal NA Cash TM Alam U Enam S Tierney P Araujo N Mozaffar FH Pestronk A Mozaffar T Seropositivity for NT5c1A antibody in sporadic inclusion body myositis predicts more severe motor, bulbar and respiratory involvement J Neurol Neurosurg Psychiatry 2016 87 373 378 10.1136/jnnp-2014-310008 25857661 38. Herbert MK Stammen-Vogelzangs J Verbeek MM Rietveld A

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Gene: NT5C1A - 5'-nucleotidase, cytosolic IA - (NCBI)

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