Analysis of the Targets and Glycosylation of Monoclonal IgAs From MGUS and Myeloma Patients.

Adrien Bosseboeuf,Jean Harb,Anne Tallet,Francis Mégraud,Nicolas Mennesson,Sylvie Hermouet,Eric Piver,Célia Seillier,Philippe Lehours,Edith Bigot-Corbel,Laureline Berthelot,Maeva Fourny,Sophie Allain-Maillet

doi:10.3389/fimmu.2020.00854

Abstract

Previous studies showed that monoclonal immunoglobulins G (IgGs) of “monoclonal gammopathy of undetermined significance” (MGUS) and myeloma were hyposialylated, thus presumably pro-inflammatory, and for about half of patients, the target of the monoclonal IgG was either a virus—Epstein–Barr virus (EBV), other herpes viruses, hepatitis C virus (HCV)—or a glucolipid, lysoglucosylceramide (LGL1), suggesting antigen-driven disease in these patients. In the present study, we show that monoclonal IgAs share these characteristics. We collected 35 sera of patients with a monoclonal IgA (6 MGUS, 29 myeloma), and we were able to purify 25 of the 35 monoclonal IgAs (6 MGUS, 19 myeloma). Monoclonal IgAs from MGUS and myeloma patients were significantly less sialylated than IgAs from healthy volunteers. When purified monoclonal IgAs were tested against infectious pathogens and LGL1, five myeloma patients had a monoclonal IgA that specifically recognized viral proteins: the core protein of HCV in one case, EBV nuclear antigen 1 (EBNA-1) in four cases (21.1% of IgA myeloma). Monoclonal IgAs from three myeloma patients reacted against LGL1. In summary, monoclonal IgAs are hyposialylated and as described for IgG myeloma, significant subsets (8/19, or 42%) of patients with IgA myeloma may have viral or self (LGL1) antigen-driven disease.

Highlights

Myeloma is preceded by an asymptomatic stage termed monoclonal gammopathy of undetermined significance (MGUS) [1,2,3,4]
All but one patients with IgA myeloma presented with bone lesions, and the International Staging System (ISS) and Durie–Salmon Staging (DSS) scores indicated that 50.0% of patients presented with ISS stage III at the time of diagnosis
No antigenic target was identified for the monoclonal IgAs from MGUS patients, but for patients with IgA myeloma, two viruses (EBV, hepatitis C virus (HCV)) were candidate targets for the monoclonal IgA of 5/19 patients (26.3%)

Summary

Introduction

Myeloma is preceded by an asymptomatic stage termed monoclonal gammopathy of undetermined significance (MGUS) [1,2,3,4]. In MGUS and myeloma, clonal plasma cells produce large quantities of a so-called “monoclonal” immunoglobulin (Ig). In MGUS, clonal plasma cells represent 30 g/L [6]. For 55–60% of MGUS and myeloma patients, the monoclonal Ig is type G, for 20–25%, it is type A, and for

Methods

Results

Conclusion