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Presented by: Dr. Sylvie Hermouet - Associate Professor in Hematology at the Medical School of Nantes
Date: May 17, 2023

Multiple myeloma (MM), its preceding stages, smoldering myeloma (SMM), and monoclonal gammopathy of undetermined significance (MGUS) are characterized by the presence of a mutated plasmacytic clone that produces large amounts of a single immunoglobulin (Ig), called monoclonal Ig. Over the years, the size of the plasmacytic clone and the quantity of monoclonal Ig increase when MGUS progresses toward SMM, then to overt MM. Thus, monoclonal Ig is a major marker of disease evolution. Yet its role in MGUS, SMM, and MM remains poorly understood, and the monoclonal Ig is not a target in the treatment of MM. Reasoning that most Ig's are produced to fight infections, we designed a new assay, called the multiplexed infectious antigen micro-array (MIAA) assay, which allows determining whether purified monoclonal Igs from MGUS, SMM, or MM patients target infectious pathogens. Using the MIAA assay, we were able to show that >50% of MGUS patients, >40% of SMM patients, and 30% of MM patients present with a monoclonal Ig that specifically recognizes a pathogen that causes chronic infection, notably Hepatitis C and B viruses (HCV, HBV), Helicobacter pylori and Herpesviruses. MGUS and MM disease in these patients is likely initiated by infection since anti-viral therapy can lead to the disappearance of antigenic stimulation, control of the plasmacytic clone, and reduced or suppressed production of the monoclonal Ig, as demonstrated recently for MM patients presenting with a monoclonal Ig specific for HCV or HBV (Front Immunol 2022, Haematologica 2023). In addition, the PEPperCHIP® Infectious Disease Epitope Microarray was used to identify sequences of Enterovirus VP1 proteins recognized by ~7% purified monoclonal Igs. In summary, this presentation describes results obtained using the MIAA assay or PEPperCHIP® Microarrays, to identify targets of monoclonal Ig's, and the importance and interest for patients of treatments that reduce or suppress the target of their monoclonal Ig, when the monoclonal Ig reacts against a treatable infectious pathogen.

Topics covered

  • The MIAA assay results: identification of monoclonal Igs that recognize pathogens causing chronic infections.
  • Anti-viral therapy has been found to control the plasmacytic clone and reduce monoclonal Ig production in MM patients.
  • How PEPperCHIP® Infectious Disease Epitope Microarray was also used to identify sequences of Enterovirus VP1 proteins recognized by a small percentage of purified monoclonal Igs.

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About the presenter

Dr. Sylvie Hermouet is an MD Ph.D., Associate Professor in Hematology at the Medical School of Nantes, in France, a Hemato-Biologist at the University Hospital of Nantes, and a Researcher at Inserm UMR1302 (INCIT), also in Nantes, specialized in the biology and diagnosis of myeloproliferative neoplasms (MPN), multiple myeloma and monoclonal gammopathies of undetermined significance (MGUS).
Member of European LeukemiaNet (MPN working group, since 2008)
Chair of MPN&MPNr-EuroNet (2009-2021) (COST Action BM0902, 2009-2013)
International Myeloma Foundation (IMF) 2020 Brian D. Novis Research Award
International Myeloma Foundation (IMF) 2021 Black Swan Research Initiative Award