{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:02:30Z","timestamp":1789009350024,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T00:00:00Z","timestamp":1589500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ligue Nationale contre le Cancer","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/501100009895","name":"Canceropole Grand Ouest","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100009895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013414","name":"Region Pays de la Loire","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100013414","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Janssen","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Chronic stimulation by infectious or self-antigens initiates subsets of monoclonal gammopathies of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple myeloma (MM). Recently, glucosylsphingosine (GlcSph) was reported to be the target of one third of monoclonal immunoglobulins (Igs). In this study of 233 patients (137 MGUS, 6 SMM, 90 MM), we analyzed the GlcSph-reactivity of monoclonal Igs and non-clonal Igs. The presence of GlcSph-reactive Igs in serum was unexpectedly frequent, detected for 103\/233 (44.2%) patients. However, GlcSph was targeted by the patient\u2019s monoclonal Ig for only 37 patients (15.9%); for other patients (44 MGUS, 22 MM), the GlcSph-reactive Igs were non-clonal. Then, the characteristics of patients were examined: compared to MM with an Epstein-Barr virus EBNA-1-reactive monoclonal Ig, MM patients with a GlcSph-reactive monoclonal Ig had a mild presentation. The inflammation profiles of patients were similar except for moderately elevated levels of 4 cytokines for patients with GlcSph-reactive Igs. In summary, our study highlights the importance of analyzing clonal Igs separately from non-clonal Igs and shows that, if autoimmune responses to GlcSph are frequent in MGUS\/SMM and MM, GlcSph presumably represents the initial pathogenic event for ~16% cases. Importantly, GlcSph-initiated MM appears to be a mild form of MM disease.<\/jats:p>","DOI":"10.3390\/cancers12051254","type":"journal-article","created":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T02:43:42Z","timestamp":1589769822000},"page":"1254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1"],"prefix":"10.3390","volume":"12","author":[{"given":"Adrien","family":"Bosseboeuf","sequence":"first","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie et Immunologie Nantes-Angers (CRCINA), Inserm, Universit\u00e9 de Nantes, Universit\u00e9 d\u2019Angers, 44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Mennesson","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie et Immunologie Nantes-Angers (CRCINA), Inserm, Universit\u00e9 de Nantes, Universit\u00e9 d\u2019Angers, 44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Allain-Maillet","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie et Immunologie Nantes-Angers (CRCINA), Inserm, Universit\u00e9 de Nantes, Universit\u00e9 d\u2019Angers, 44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Tallet","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie, Centre Hospitalier Universitaire (CHU) Tours, 37000 Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Piver","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie, Centre Hospitalier Universitaire (CHU) Tours, 37000 Tours, France"},{"name":"Inserm UMR966, 37000 Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Decaux","sequence":"additional","affiliation":[{"name":"Internal Medicine, CHU Rennes, 35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5503-4078","authenticated-orcid":false,"given":"Caroline","family":"Moreau","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie, CHU Rennes, 35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Moreau","sequence":"additional","affiliation":[{"name":"Hematology Department, CHU Nantes, 44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6704-8699","authenticated-orcid":false,"given":"Philippe","family":"Lehours","sequence":"additional","affiliation":[{"name":"Laboratoire de Bact\u00e9riologie, CHU Bordeaux, 33000 Bordeaux, France"},{"name":"Inserm U1053, Universit\u00e9 de Bordeaux, 33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"M\u00e9graud","sequence":"additional","affiliation":[{"name":"Laboratoire de Bact\u00e9riologie, CHU Bordeaux, 33000 Bordeaux, France"},{"name":"Inserm U1053, Universit\u00e9 de Bordeaux, 33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9ry","family":"Salle","sequence":"additional","affiliation":[{"name":"M\u00e9decine Interne et Maladies Syst\u00e9miques, CHU Amiens, 80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2760-8740","authenticated-orcid":false,"given":"Edith","family":"Bigot-Corbel","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie et Immunologie Nantes-Angers (CRCINA), Inserm, Universit\u00e9 de Nantes, Universit\u00e9 d\u2019Angers, 44000 Nantes, France"},{"name":"Laboratoire de Biochimie, CHU Nantes, 44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Harb","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie et Immunologie Nantes-Angers (CRCINA), Inserm, Universit\u00e9 de Nantes, Universit\u00e9 d\u2019Angers, 44000 Nantes, France"},{"name":"Laboratoire de Biochimie, CHU Nantes, 44000 Nantes, France"},{"name":"Centre de Recherche en Transplantation et Immunologie (CRTI), UMR1064, Inserm, Universit\u00e9 de Nantes, 44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Hermouet","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie et Immunologie Nantes-Angers (CRCINA), Inserm, Universit\u00e9 de Nantes, Universit\u00e9 d\u2019Angers, 44000 Nantes, France"},{"name":"Laboratoire d\u2019H\u00e9matologie, CHU Nantes, 44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1182\/blood-2016-09-692954","article-title":"MGUS to myeloma: A mysterious gammopathy of underexplored significance","volume":"128","author":"Dhodapkar","year":"2016","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1056\/NEJMoa1709974","article-title":"Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance","volume":"378","author":"Kyle","year":"2018","journal-title":"N. 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