{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:38:39Z","timestamp":1787027919769,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T00:00:00Z","timestamp":1636761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: The detection of anti-acetylcholine receptor (AChR) and anti-muscle-specific tyrosine kinase (MuSK) antibodies is useful in myasthenia gravis (MG) diagnosis and management. BIOCHIP mosaic-based indirect immunofluorescence is a novel analytical method, which employs the simultaneous detection of anti-AChR and anti-MuSK antibodies in a single miniature incubation field. In this study, we compare, for the first time, the BIOCHIP MG mosaic with conventional enzyme-linked immunosorbent assay (ELISA) in the diagnosis of MG. Methods: A total of 71 patients with MG diagnosis were included in the study. Anti-AChR and anti-MuSK antibodies were measured separately by two different ELISA and simultaneously by BIOCHIP. The results were then compared. Results: The overall concordance between ELISA and BIOCHIP for anti-AChR reactivity was 74%. Cohen\u2019s kappa was 0.51 (95% CI 0.32\u20130.71), which corresponds to 90% of the maximum possible kappa (0.57), given the observed marginal frequencies. The overall concordance for anti-MuSK reactivity was 84%. Cohen\u2019s kappa was 0.11 (95% CI 0.00\u20130.36), which corresponds to 41% of the maximum possible kappa (0.27). Conclusion: The overall concordance among assays is not optimal.<\/jats:p>","DOI":"10.3390\/diagnostics11112098","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T20:48:36Z","timestamp":1636922916000},"page":"2098","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Comparative Analysis of BIOCHIP Mosaic-Based Indirect Immunofluorescence with Enzyme-Linked Immunosorbent Assay for Diagnosing Myasthenia Gravis"],"prefix":"10.3390","volume":"11","author":[{"given":"Caterina Maria","family":"Gambino","sequence":"first","affiliation":[{"name":"Clinical Molecular Medicine and Laboratory Medicine, Institute of Clinical Biochemistry, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Agnello","sequence":"additional","affiliation":[{"name":"Clinical Molecular Medicine and Laboratory Medicine, Institute of Clinical Biochemistry, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna","family":"Lo Sasso","sequence":"additional","affiliation":[{"name":"Clinical Molecular Medicine and Laboratory Medicine, Institute of Clinical Biochemistry, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Scazzone","sequence":"additional","affiliation":[{"name":"Clinical Molecular Medicine and Laboratory Medicine, Institute of Clinical Biochemistry, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria Vincenza","family":"Giglio","sequence":"additional","affiliation":[{"name":"Clinical Molecular Medicine and Laboratory Medicine, Institute of Clinical Biochemistry, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Candore","sequence":"additional","affiliation":[{"name":"Clinical Molecular Medicine and Laboratory Medicine, Institute of Clinical Biochemistry, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Ciaccio","sequence":"additional","affiliation":[{"name":"Unit of Clinical Biochemistry, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9805-1655","authenticated-orcid":false,"given":"Vincenzo","family":"Di Stefano","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Biomedicine, Neurosciences and Advanced Diagnostics, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Brighina","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Biomedicine, Neurosciences and Advanced Diagnostics, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9991-7502","authenticated-orcid":false,"given":"Matteo","family":"Vidali","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6120-9041","authenticated-orcid":false,"given":"Marcello","family":"Ciaccio","sequence":"additional","affiliation":[{"name":"Clinical Molecular Medicine and Laboratory Medicine, Institute of Clinical Biochemistry, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"},{"name":"Department of Laboratory Medicine, Azienda Ospedaliera Universitaria Policlinico \u201cP. Giaccone\u201d, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jaut.2013.12.011","article-title":"Myasthenia gravis: A comprehensive review of immune dysregulation and etiological mechanisms","volume":"52","year":"2014","journal-title":"J. Autoimmun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/S1474-4422(15)00145-3","article-title":"Myasthenia gravis: Subgroup classification and therapeutic strategies","volume":"14","author":"Gilhus","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41572-019-0079-y","article-title":"Myasthenia gravis","volume":"5","author":"Gilhus","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1056\/NEJMra1602678","article-title":"Myasthenia Gravis","volume":"375","author":"Gilhus","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1080\/14737159.2021.1927715","article-title":"Improving laboratory diagnostics in myasthenia gravis","volume":"21","author":"Gastaldi","year":"2021","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.autrev.2013.03.001","article-title":"Pathophysiology of myasthenia gravis with antibodies to the acetylcholine receptor, muscle-specific kinase and low-density lipoprotein receptor-related protein 4","volume":"12","author":"Verschuuren","year":"2013","journal-title":"Autoimmun. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00415-011-6194-7","article-title":"Anti-LRP4 autoantibodies in AChR- and MuSK-antibody-negative myasthenia gravis","volume":"259","author":"Pevzner","year":"2012","journal-title":"J. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"707","DOI":"10.3389\/fimmu.2020.00707","article-title":"Muscle-Specific Kinase Myasthenia Gravis","volume":"11","author":"Borges","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/0090-1229(77)90027-7","article-title":"An assay for antibodies to human acetylcholine receptor in serum from patients with myasthenia gravis","volume":"7","author":"Lindstrom","year":"1977","journal-title":"Clin. Immunol. Immunopathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.cccn.2004.05.008","article-title":"Muscle-specific receptor tyrosine kinase autoantibodies--A new immunoprecipitation assay","volume":"348","author":"Matthews","year":"2004","journal-title":"Clin. Chim. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.cccn.2005.05.035","article-title":"A sensitive non-isotopic assay for acetylcholine receptor autoantibodies","volume":"364","author":"Hewer","year":"2006","journal-title":"Clin. Chim. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1093\/brain\/awn092","article-title":"IgG1 antibodies to acetylcholine receptors in \u2018seronegative\u2019 myasthenia gravis","volume":"131","author":"Leite","year":"2008","journal-title":"Brain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jneuroim.2008.06.020","article-title":"Towards antigen-specific apheresis of pathogenic autoantibodies as a further step in the treatment of myasthenia gravis by plasmapheresis","volume":"201\u2013202","author":"Zisimopoulou","year":"2008","journal-title":"J. Neuroimmunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1212\/WNL.0000000000011124","article-title":"International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update","volume":"96","author":"Narayanaswami","year":"2021","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"371","DOI":"10.3109\/08916930903541208","article-title":"Diagnostic use of autoantibodies in myasthenia gravis","volume":"43","author":"Leite","year":"2010","journal-title":"Autoimmunity"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"596621","DOI":"10.3389\/fneur.2020.596621","article-title":"Immunopathology of Autoimmune Myasthenia Gravis: Implications for Improved Testing Algorithms and Treatment Strategies","volume":"11","author":"Frykman","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"596981","DOI":"10.3389\/fneur.2020.596981","article-title":"Myasthenia Gravis: Autoantibody Specificities and Their Role in MG Management","volume":"11","author":"Lazaridis","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/(SICI)1097-4598(200004)23:4<453::AID-MUS3>3.0.CO;2-O","article-title":"Acetylcholine receptors and myasthenia","volume":"23","author":"Lindstrom","year":"2000","journal-title":"Muscle Nerve"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1136\/jnnp.48.12.1246","article-title":"Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: Results in 153 validated cases and 2967 diagnostic assays","volume":"48","author":"Vincent","year":"1985","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e1426","DOI":"10.1212\/WNL.0000000000010209","article-title":"Subgroup stratification and outcome in recently diagnosed generalized myasthenia gravis","volume":"95","author":"Tomschik","year":"2020","journal-title":"Neurology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/S1474-4422(16)00033-8","article-title":"Myasthenia gravis: Subgroup classifications","volume":"15","author":"Kohler","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1756285617749134","DOI":"10.1177\/1756285617749134","article-title":"When myasthenia gravis is deemed refractory: Clinical signposts and treatment strategies","volume":"11","author":"Mantegazza","year":"2018","journal-title":"Ther Adv Neurol Disord."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"981","DOI":"10.3389\/fneur.2020.00981","article-title":"From Traditional to Targeted Immunotherapy in Myasthenia Gravis: Prospects for Research","volume":"11","author":"Mantegazza","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1097\/WCO.0000000000000858","article-title":"Progress in the therapy of myasthenia gravis: Getting closer to effective targeted immunotherapies","volume":"33","author":"Dalakas","year":"2020","journal-title":"Curr. Opin. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"116690","DOI":"10.1016\/j.jns.2020.116690","article-title":"Differential response to rituximab in anti-AChR and anti-MuSK positive myasthenia gravis patients: A single-center retrospective study","volume":"411","author":"Litchman","year":"2020","journal-title":"J. Neurol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"212","DOI":"10.3389\/fimmu.2020.00212","article-title":"Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics","volume":"11","author":"Lazaridis","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jneuroim.2008.01.013","article-title":"Clinical fluctuations in MuSK myasthenia gravis are related to antigen-specific IgG4 instead of IgG1","volume":"195","author":"Niks","year":"2008","journal-title":"J. Neuroimmunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/nyas.13561","article-title":"IgG4-mediated autoimmune diseases: A niche of antibody-mediated disorders","volume":"1413","author":"Huijbers","year":"2018","journal-title":"Ann. NY Acad. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ncl.2018.01.004","article-title":"Muscle-Specific Tyrosine Kinase and Myasthenia Gravis Owing to Other Antibodies","volume":"36","author":"Rivner","year":"2018","journal-title":"Neurol. Clin."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/j.1749-6632.1987.tb51301.x","article-title":"The membrane attack complex of complement at the endplate in myasthenia gravis","volume":"505","author":"Engel","year":"1987","journal-title":"Ann. NY Acad. Sci."},{"key":"ref_31","first-page":"82","article-title":"Acetylcholine receptor antibody in myasthenia gravis: Predominance of IgG subclasses 1 and 3","volume":"67","author":"Nielsen","year":"1987","journal-title":"Clin. Exp. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/labmed\/lmy038","article-title":"A Simple, Rapid and Non-Radiolabeled Immune Assay to Detect Anti-AChR Antibodies in Myasthenia Gravis","volume":"50","author":"Bokoliya","year":"2019","journal-title":"Lab. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jim.2018.06.016","article-title":"Immunostick ELISA for rapid and easy diagnosis of myasthenia gravis","volume":"460","author":"Trakas","year":"2018","journal-title":"J. Immunol. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.autrev.2013.03.002","article-title":"Serological diagnostics in myasthenia gravis based on novel assays and recently identified antigens","volume":"12","author":"Zisimopoulou","year":"2013","journal-title":"Autoimmun. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s12264-012-1256-0","article-title":"Clinical significance of detection of antibodies to fetal and adult acetylcholine receptors in myasthenia gravis","volume":"28","author":"Shi","year":"2012","journal-title":"Neurosci. Bull."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1172\/JCI119048","article-title":"Association of arthrogryposis multiplex congenita with maternal antibodies inhibiting fetal acetylcholine receptor function","volume":"98","author":"Riemersma","year":"1966","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"14426","DOI":"10.1038\/s41598-017-14350-8","article-title":"Characterization of an anti-fetal AChR monoclonal antibody isolated from a myasthenia gravis patient","volume":"7","author":"Saxena","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jim.2019.03.009","article-title":"The use of BIOCHIP technique in diagnosis of different types of pemphigus: Vulgaris and foliaceus","volume":"468","author":"Adaszewska","year":"2019","journal-title":"J. Immunol. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1159\/000339776","article-title":"Anti-skin specific autoantibodies detected by a new immunofluorescence multiplex biochip method in patients with autoimmune bullous diseases","volume":"225","author":"Tampoia","year":"2012","journal-title":"Dermatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105","DOI":"10.4103\/idoj.IDOJ_156_19","article-title":"Comparative Analysis of BIOCHIP Mosaic-based Indirect Immunofluorescence with Direct Immunofluorescence in Diagnosis of Autoimmune Bullous Diseases: A Cross-Sectional Study","volume":"12","author":"Arunprasath","year":"2021","journal-title":"Indian Dermatol. Online J."},{"key":"ref_41","first-page":"49","article-title":"Serological diagnosis of autoimmune bullous skin diseases: Prospective comparison of the BIOCHIP mosaic-based indirect immunofluorescence technique with the conventional multi-step single test strategy","volume":"7","author":"Rentzsch","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ijwd.2017.10.001","article-title":"New biochip immunofluorescence test for the serological diagnosis of pemphigus vulgaris and foliaceus: A review of the literature","volume":"4","author":"Xuan","year":"2018","journal-title":"Int. J. Womens Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/jdv.15770","article-title":"Validation of the BIOCHIP test for the diagnosis of bullous pemphigoid, pemphigus vulgaris and pemphigus foliaceus","volume":"34","author":"Yang","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Granieri, L., Marnetto, F., Valentino, P., Frau, J., Patanella, A.K., Nytrova, P., Sola, P., Capobianco, M., Jarius, S., and Bertolotto, A. (2012). Evaluation of a multiparametric immunofluorescence assay for standardization of neuromyelitis optica serology. 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