FCGR3A F158V alleles frequency differs in multiple myeloma patients from healthy population

FCGR3A presents a single nucleotide polymorphism at location 158 (V/F), which affects its binding to the fragment crystallizable (Fc) of antibodies (Abs). FcγRIIIa-158 V allotype has the highest affinity and is associated with a better clinical response to IgG1 monoclonal Abs (mAb) treatment. We com...

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Main Authors: Michaël Constantinides, Nicolas Robert, Caroline Multrier, Loïs Coënon, Mauricio Campos-Mora, Carine Jacquard, Fei Gao, Sara Zemiti, Jessy Presumey, Guillaume Cartron, Jérome Moreaux, Martin Villalba
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:OncoImmunology
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Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2024.2388306
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author Michaël Constantinides
Nicolas Robert
Caroline Multrier
Loïs Coënon
Mauricio Campos-Mora
Carine Jacquard
Fei Gao
Sara Zemiti
Jessy Presumey
Guillaume Cartron
Jérome Moreaux
Martin Villalba
author_facet Michaël Constantinides
Nicolas Robert
Caroline Multrier
Loïs Coënon
Mauricio Campos-Mora
Carine Jacquard
Fei Gao
Sara Zemiti
Jessy Presumey
Guillaume Cartron
Jérome Moreaux
Martin Villalba
author_sort Michaël Constantinides
collection DOAJ
description FCGR3A presents a single nucleotide polymorphism at location 158 (V/F), which affects its binding to the fragment crystallizable (Fc) of antibodies (Abs). FcγRIIIa-158 V allotype has the highest affinity and is associated with a better clinical response to IgG1 monoclonal Abs (mAb) treatment. We compared the allele frequency of FCGR3A-F158V polymorphism in cohorts of patients with B-cell lymphoproliferative disorders, including multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), non-Hodgkin lymphoma (NHL), and B-cell chronic leukemia (B-CLL). FCGR3A-158F homozygous were enriched and tended to be in MM and MGUS patients, respectively; but neither in B-CLL nor in NHL patients. We identified a significantly lower concentration of CD8 T-cells and resting memory CD4 T-cells in MM patients bone marrow with the F/F genotype, associated with an increase in the macrophage percentage. In contrast, natural killer cells increased in V/V homozygous patients. This suggests a deregulation of the immune microenvironment in FCGR3A-F/F homozygous patients. However, we did not observe difference in response following treatment combining chemotherapy associated or not with daratumumab, an IgG1 mAb direct against CD38. Our findings suggest that FCGR3A F158V polymorphism can regulate the immune environment and affect the development of tumor plasma cells.
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spelling doaj-art-41bd2ee094e54a0abe73a44b834b684b2024-12-03T13:49:34ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2024.2388306FCGR3A F158V alleles frequency differs in multiple myeloma patients from healthy populationMichaël Constantinides0Nicolas Robert1Caroline Multrier2Loïs Coënon3Mauricio Campos-Mora4Carine Jacquard5Fei Gao6Sara Zemiti7Jessy Presumey8Guillaume Cartron9Jérome Moreaux10Martin Villalba11IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, FranceDepartment of Biological Hematology, CHU Montpellier, Montpellier, FranceIRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, FranceIRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, FranceIRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, FranceIRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, FranceIRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, FranceIRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, FranceIRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, FranceDepartment of Clinical Hematology, CHU Montpellier, Montpellier, FranceDepartment of Biological Hematology, CHU Montpellier, Montpellier, FranceIRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, FranceFCGR3A presents a single nucleotide polymorphism at location 158 (V/F), which affects its binding to the fragment crystallizable (Fc) of antibodies (Abs). FcγRIIIa-158 V allotype has the highest affinity and is associated with a better clinical response to IgG1 monoclonal Abs (mAb) treatment. We compared the allele frequency of FCGR3A-F158V polymorphism in cohorts of patients with B-cell lymphoproliferative disorders, including multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), non-Hodgkin lymphoma (NHL), and B-cell chronic leukemia (B-CLL). FCGR3A-158F homozygous were enriched and tended to be in MM and MGUS patients, respectively; but neither in B-CLL nor in NHL patients. We identified a significantly lower concentration of CD8 T-cells and resting memory CD4 T-cells in MM patients bone marrow with the F/F genotype, associated with an increase in the macrophage percentage. In contrast, natural killer cells increased in V/V homozygous patients. This suggests a deregulation of the immune microenvironment in FCGR3A-F/F homozygous patients. However, we did not observe difference in response following treatment combining chemotherapy associated or not with daratumumab, an IgG1 mAb direct against CD38. Our findings suggest that FCGR3A F158V polymorphism can regulate the immune environment and affect the development of tumor plasma cells.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2388306FCGR3A polymorphismFcγRIIIa/CD16amonoclonal gammopathy of undetermined significance (MGUS)multiple myeloma (MM)tumor environment
spellingShingle Michaël Constantinides
Nicolas Robert
Caroline Multrier
Loïs Coënon
Mauricio Campos-Mora
Carine Jacquard
Fei Gao
Sara Zemiti
Jessy Presumey
Guillaume Cartron
Jérome Moreaux
Martin Villalba
FCGR3A F158V alleles frequency differs in multiple myeloma patients from healthy population
OncoImmunology
FCGR3A polymorphism
FcγRIIIa/CD16a
monoclonal gammopathy of undetermined significance (MGUS)
multiple myeloma (MM)
tumor environment
title FCGR3A F158V alleles frequency differs in multiple myeloma patients from healthy population
title_full FCGR3A F158V alleles frequency differs in multiple myeloma patients from healthy population
title_fullStr FCGR3A F158V alleles frequency differs in multiple myeloma patients from healthy population
title_full_unstemmed FCGR3A F158V alleles frequency differs in multiple myeloma patients from healthy population
title_short FCGR3A F158V alleles frequency differs in multiple myeloma patients from healthy population
title_sort fcgr3a f158v alleles frequency differs in multiple myeloma patients from healthy population
topic FCGR3A polymorphism
FcγRIIIa/CD16a
monoclonal gammopathy of undetermined significance (MGUS)
multiple myeloma (MM)
tumor environment
url https://www.tandfonline.com/doi/10.1080/2162402X.2024.2388306
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