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Article

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

1
Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Inserm, Université de Nantes, Université d’Angers, 44000 Nantes, France
2
Laboratoire de Biochimie, Centre Hospitalier Universitaire (CHU) Tours, 37000 Tours, France
3
Inserm UMR966, 37000 Tours, France
4
Internal Medicine, CHU Rennes, 35000 Rennes, France
5
Laboratoire de Biochimie, CHU Rennes, 35000 Rennes, France
6
Hematology Department, CHU Nantes, 44000 Nantes, France
7
Laboratoire de Bactériologie, CHU Bordeaux, 33000 Bordeaux, France
8
Inserm U1053, Université de Bordeaux, 33000 Bordeaux, France
9
Médecine Interne et Maladies Systémiques, CHU Amiens, 80000 Amiens, France
10
Laboratoire de Biochimie, CHU Nantes, 44000 Nantes, France
11
Centre de Recherche en Transplantation et Immunologie (CRTI), UMR1064, Inserm, Université de Nantes, 44000 Nantes, France
12
Laboratoire d’Hématologie, CHU Nantes, 44000 Nantes, France
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(5), 1254; https://doi.org/10.3390/cancers12051254
Received: 4 April 2020 / Revised: 12 May 2020 / Accepted: 12 May 2020 / Published: 15 May 2020
(This article belongs to the Special Issue The Asymptomatic Version of Myeloma: MGUS and Smoldering Myeloma)
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. View Full-Text
Keywords: multiple myeloma; monoclonal gammopathy of undetermined significance (MGUS); monoclonal immunoglobulin; antigen specificity; auto-antigen; glucosylsphingosine (GlcSph); lysoglucosyl-ceramide (LGL1); sialylation; cytokine; inflammation; interleukin-13 (IL-13); interleukin-17 (IL-17); interleukin-26 (IL-26) multiple myeloma; monoclonal gammopathy of undetermined significance (MGUS); monoclonal immunoglobulin; antigen specificity; auto-antigen; glucosylsphingosine (GlcSph); lysoglucosyl-ceramide (LGL1); sialylation; cytokine; inflammation; interleukin-13 (IL-13); interleukin-17 (IL-17); interleukin-26 (IL-26)
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MDPI and ACS Style

Bosseboeuf, A.; Mennesson, N.; Allain-Maillet, S.; Tallet, A.; Piver, E.; Decaux, O.; Moreau, C.; Moreau, P.; Lehours, P.; Mégraud, F.; Salle, V.; Bigot-Corbel, E.; Harb, J.; Hermouet, S. Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1. Cancers 2020, 12, 1254. https://doi.org/10.3390/cancers12051254

AMA Style

Bosseboeuf A, Mennesson N, Allain-Maillet S, Tallet A, Piver E, Decaux O, Moreau C, Moreau P, Lehours P, Mégraud F, Salle V, Bigot-Corbel E, Harb J, Hermouet S. Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1. Cancers. 2020; 12(5):1254. https://doi.org/10.3390/cancers12051254

Chicago/Turabian Style

Bosseboeuf, Adrien, Nicolas Mennesson, Sophie Allain-Maillet, Anne Tallet, Eric Piver, Olivier Decaux, Caroline Moreau, Philippe Moreau, Philippe Lehours, Francis Mégraud, Valéry Salle, Edith Bigot-Corbel, Jean Harb, and Sylvie Hermouet. 2020. "Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1" Cancers 12, no. 5: 1254. https://doi.org/10.3390/cancers12051254

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