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Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens

Adrien Bosseboeuf 1 Delphine Féron 1 Anne Tallet 2 Cédric Rossi 3 Cathy Charlier 4 Laurent Garderet 5, 6, 7 Denis Caillot 3 Philippe Moreau 8 Marina Cardó-Vila 9, 10 Renata Pasqualini 9, 10 Wadih Arap 10, 11 Alfreda Destea Nelson 10, 12 Bridget S Wilson 10, 12 Hélène Perreault 13 Eric Piver 2, 14 Pierre Weigel 4 François Girodon 3 Jean Harb 15, 16 Edith Bigot-Corbel 1, 16 Sylvie Hermouet 1, 17 
Abstract : Subsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori. However, the association between infection and the immunoglobulin-secreting (Ig-secreting) B proliferative disorders remains largely unresolved. We investigated whether the monoclonal IgG (mc IgG) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) targets infectious pathogens. Antigen specificity of purified mc IgG from a large patient cohort (n = 244) was determined using a multiplex infectious-antigen array (MIAA), which screens for reactivity to purified antigens or lysates from 9 pathogens. Purified mc IgG from 23.4% of patients (57 of 244) specifically recognized 1 pathogen in the MIAA. EBV was the most frequent target (15.6%), with 36 of 38 mc IgGs recognizing EBV nuclear antigen-1 (EBNA-1). MM patients with EBNA-1-specific mc IgG (14.0%) showed substantially greater bone marrow plasma cell infiltration and higher β2-microglobulin and inflammation/infection-linked cytokine levels compared with other smoldering myeloma/MM patients. Five other pathogens were the targets of mc IgG: herpes virus simplex-1 (2.9%), varicella zoster virus (1.6%), cytomegalovirus (0.8%), hepatitis C virus (1.2%), and H. pylori (1.2%). We conclude that a dysregulated immune response to infection may underlie disease onset and/or progression of MGUS and MM for subsets of patients.
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Submitted on : Friday, November 3, 2017 - 10:43:44 AM
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Adrien Bosseboeuf, Delphine Féron, Anne Tallet, Cédric Rossi, Cathy Charlier, et al.. Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens. JCI Insight, American Society for Clinical Investigation, 2017, 2 (19), Epub ahead of print. ⟨10.1172/jci.insight.95367⟩. ⟨inserm-01628286⟩



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