title: Monoclonal paraprotein influences baseline B-cell repertoire diversity and perturbates influenza vaccination-induced B-cell response.
abstract: Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasma cells in the bone marrow, secreting monoclonal (M) paraprotein. It is associated with increased susceptibility to infections, which may reflect altered B-cell repertoire. To investigate this, we examined the immunoglobulin (Ig) M, IgG, and IgA B-cell repertoire diversity in MGUS at baseline and after influenza vaccination (n = 16) in comparison with healthy controls (HCs; n = 16). The Complementary Determining Region 3 region of the immunoglobulin heavy chain variable region gene was amplified and B-cell spectratypes analyzed by high-resolution electrophoresis. Spectratype Gaussian distribution, kurtosis, and skewness were quantified to measure repertoire shifts. Both HC and MGUS baseline spectratypes show interindividual variability that is more pronounced in the IGHG and IGHA repertoires. Overall, baseline B-cell repertoire is more altered in MGUS, with oligoclonality observed in 50% (p = 0.01). Postvaccination, significant differences emerged in MGUS in relation to M-protein levels. High M-protein concentration is associated with a more oligoclonal IgG and IgA response at day 7 postvaccination, and, in contrast to HCs, vaccination also induced significant perturbations in the MGUS IgM repertoire at day 7 (p = 0.005). Monoclonal expansion in MGUS thus has an effect on the baseline B-cell repertoire and influences the recruited repertoire upon vaccination.
authors: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Cancer Sciences Academic Unit, University of Southampton School of Medicine, Southampton, United Kingdom.
authors: Sarah M
authors: SM
authors: Tete
authors: Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
authors: David
authors: D
authors: Kipling
authors: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Johanna
authors: J
authors: Westra
authors: Molecular Virology Section, Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Aalzen
authors: A
authors: de Haan
authors: Department of Internal Medicine and Rheumatology, Martini Ziekenhuis, Groningen, The Netherlands.
authors: Marc
authors: M
authors: Bijl
authors: Peter Gorer Department of Immunobiology, King's College London School of Medicine, London, United Kingdom.
authors: Deborah K
authors: DK
authors: Dunn-Walters
authors: Cancer Sciences Academic Unit, University of Southampton School of Medicine, Southampton, United Kingdom.
authors: Surinder S
authors: SS
authors: Sahota
authors: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: n.a.bos@umcg.nl.
authors: Nicolaas A
authors: NA
authors: Bos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000276:immunology; D010266:Paraproteins / Q000502:physiology*; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains; D007252:Influenza Vaccines; D010266:Paraproteins