{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:16:19Z","timestamp":1791270979370,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005743","name":"Universit\u00e0 Cattolica del Sacro Cuore","doi-asserted-by":"publisher","award":["Linea D1"],"award-info":[{"award-number":["Linea D1"]}],"id":[{"id":"10.13039\/501100005743","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myasthenia gravis with antibodies (Abs) against the muscle-specific tyrosine kinase (MuSK) is a rare autoimmune disorder (AD) of the neuromuscular junction (NMJ) and represents a prototype of AD with proven IgG4-mediated pathogenicity. Thanks to the mechanism of Fab-arm exchange (FAE) occurring in vivo, resulting MuSK IgG4 k\/\u03bb Abs increase their interference on NMJ and pathogenicity. The characterization of hybrid MuSK IgG4 as a biomarker for MG management is poorly investigated. Here, we evaluated total IgG4, hybrid IgG4 k\/\u03bb, and the hybrid\/total ratio in 14 MuSK-MG sera in comparison with 24 from MG with Abs against acetylcholine receptor (AChR) that represents the not IgG4-mediated MG form. In both subtypes of MG, we found that the hybrid\/total ratio reflects distribution reported in normal individuals; instead, when we correlated the hybrid\/total ratio with specific immune-reactivity we found a positive correlation only with anti-MuSK titer, with a progressive increase of hybrid\/total mean values with increasing disease severity, indirectly confirming that most part of hybrid IgG4 molecules are engaged in the anti-MuSK pathogenetic immune-reactivity. Further analysis is necessary to strengthen the significance of this less unknown biomarker, but we retain it is full of a diagnostic-prognostic powerful potential for the management of MuSK-MG.<\/jats:p>","DOI":"10.3390\/ijms22179142","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T22:12:22Z","timestamp":1629843142000},"page":"9142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Laboratory Investigation of Hybrid IgG4 k\/\u03bb in MuSK Positive Myasthenia Gravis"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8328-2570","authenticated-orcid":false,"given":"Umberto","family":"Basile","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8720-6284","authenticated-orcid":false,"given":"Cecilia","family":"Napodano","sequence":"additional","affiliation":[{"name":"Synlab Data Medica, 35133 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Gulli","sequence":"additional","affiliation":[{"name":"Laboratorio di Patologia Clinica, Ospedale Madre Giuseppina Vannini, 00177 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krizia","family":"Pocino","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Complessa Patologia Clinica, Ospedale Generale di Zona, San Pietro Fatebenefratelli, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Di Santo","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze, Sezione di Fisica, Fondazione Policlinico \u201cA. Gemelli\u201d IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Todi","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia Traslazionale, Sezione di Patologia Generale, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Basile","sequence":"additional","affiliation":[{"name":"Clinical Pathology Unit and Cancer Biobank, Department of Research, Advanced Diagnostics and Technological Innovation, IFO-Regina Elena National Cancer Institute, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Provenzano","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia Traslazionale, Sezione di Patologia Generale, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Ciasca","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze, Sezione di Fisica, Fondazione Policlinico \u201cA. Gemelli\u201d IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariapaola","family":"Marino","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia Traslazionale, Sezione di Patologia Generale, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Immunological Role of IgG Subclasses","volume":"11","author":"Napodano","year":"2020","journal-title":"Immunol. 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