TY - JOUR
T1 - Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens
AU - Bosseboeuf, Adrien
AU - Feron, Delphine
AU - Tallet, Anne
AU - Rossi, Cédric
AU - Charlier, Cathy
AU - Garderet, Laurent
AU - Caillot, Denis
AU - Moreau, Philippe
AU - Cardó-Vila, Marina
AU - Pasqualini, Renata
AU - Arap, Wadih
AU - Nelson, Alfreda Destea
AU - Wilson, Bridget S.
AU - Perreault, Hélène
AU - Piver, Eric
AU - Weigel, Pierre
AU - Girodon, François
AU - Harb, Jean
AU - Bigot-Corbel, Edith
AU - Hermouet, Sylvie
N1 - Funding Information:
The study was supported by grant number 2010-088 from Institut National du Cancer (INCa), to SH and EBC (2010–2012); by a grant from the Comités Départementaux of Loire-Atlantique, Maine et Loire, Vendée and Finistère from the Ligue Nationale contre le Cancer, to EBC (2013–2014); by a grant from the Can-céropôle Grand Ouest and Région Pays de la Loire, to SH (2015–2016); by a grant from the Cancéropôle Grand Ouest and Région Centre, to EP (2015–2016); by NIH P50GM085273 to BW; and awards from the Gillson-Longenbaugh Foundation to RP and WA. This work has been funded, in part, by a UNM Cancer Center Support Grant (P30 CA118100) to RP and WA. The INCa financed the salary of DF (2011-2012), the Cancéropôle Grand Ouest and Région Pays de la Loire financed the salary of AB (HII-GO project, 2015-2016) and the Academic Science Education and Research Training-Institutional Research and Academic Career Development Award (ASERT IRACDA, grant number NIGMS K12 GM088021) supported the salary of Alfreda Nelson.
Publisher Copyright:
© 2017 American Society for Clinical Investigation. All rights reserved.
PY - 2017/10/5
Y1 - 2017/10/5
N2 - 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.
AB - 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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U2 - 10.1172/jci.insight.95367
DO - 10.1172/jci.insight.95367
M3 - Article
C2 - 28978808
AN - SCOPUS:85031762798
VL - 2
JO - JCI insight
JF - JCI insight
SN - 2379-3708
IS - 19
M1 - e95367
ER -