Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens.
Fiche publication
Date publication
octobre 2017
Journal
JCI insight
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CAILLOT Denis, Pr GIRODON François, Dr ROSSI Cédric
Tous les auteurs :
Bosseboeuf A, Feron D, Tallet A, Rossi C, Charlier C, Garderet L, Caillot D, Moreau P, Cardó-Vila M, Pasqualini R, Arap W, Nelson AD, Wilson BS, Perreault H, Piver E, Weigel P, Girodon F, Harb J, Bigot-Corbel E, Hermouet S
Lien Pubmed
Résumé
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.
Référence
JCI Insight. 2017 Oct;2(19):