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Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1

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 immunoglob...

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Autores principales: Bosseboeuf, Adrien, Mennesson, Nicolas, Allain-Maillet, Sophie, Tallet, Anne, Piver, Eric, Decaux, Olivier, Moreau, Caroline, Moreau, Philippe, Lehours, Philippe, Mégraud, Francis, Salle, Valéry, Bigot-Corbel, Edith, Harb, Jean, Hermouet, Sylvie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281552/
https://www.ncbi.nlm.nih.gov/pubmed/32429322
http://dx.doi.org/10.3390/cancers12051254
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author Bosseboeuf, Adrien
Mennesson, Nicolas
Allain-Maillet, Sophie
Tallet, Anne
Piver, Eric
Decaux, Olivier
Moreau, Caroline
Moreau, Philippe
Lehours, Philippe
Mégraud, Francis
Salle, Valéry
Bigot-Corbel, Edith
Harb, Jean
Hermouet, Sylvie
author_facet Bosseboeuf, Adrien
Mennesson, Nicolas
Allain-Maillet, Sophie
Tallet, Anne
Piver, Eric
Decaux, Olivier
Moreau, Caroline
Moreau, Philippe
Lehours, Philippe
Mégraud, Francis
Salle, Valéry
Bigot-Corbel, Edith
Harb, Jean
Hermouet, Sylvie
author_sort Bosseboeuf, Adrien
collection PubMed
description 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’s 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.
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spelling pubmed-72815522020-06-17 Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1 Bosseboeuf, Adrien Mennesson, Nicolas Allain-Maillet, Sophie Tallet, Anne Piver, Eric Decaux, Olivier Moreau, Caroline Moreau, Philippe Lehours, Philippe Mégraud, Francis Salle, Valéry Bigot-Corbel, Edith Harb, Jean Hermouet, Sylvie Cancers (Basel) Article 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’s 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. MDPI 2020-05-15 /pmc/articles/PMC7281552/ /pubmed/32429322 http://dx.doi.org/10.3390/cancers12051254 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bosseboeuf, Adrien
Mennesson, Nicolas
Allain-Maillet, Sophie
Tallet, Anne
Piver, Eric
Decaux, Olivier
Moreau, Caroline
Moreau, Philippe
Lehours, Philippe
Mégraud, Francis
Salle, Valéry
Bigot-Corbel, Edith
Harb, Jean
Hermouet, Sylvie
Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1
title Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1
title_full Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1
title_fullStr Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1
title_full_unstemmed Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1
title_short Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1
title_sort characteristics of mgus and multiple myeloma according to the target of monoclonal immunoglobulins, glucosylsphingosine, or epstein-barr virus ebna-1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281552/
https://www.ncbi.nlm.nih.gov/pubmed/32429322
http://dx.doi.org/10.3390/cancers12051254
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