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Monoclonal paraprotein influences baseline B-cell repertoire diversity and perturbates influenza vaccination-induced B-cell response

Tete, SM, Kipling, D, Westra, J, de Haan, A, Bijl, M, Dunn-Walters, D, Sahota, SS and Bos, NA (2015) Monoclonal paraprotein influences baseline B-cell repertoire diversity and perturbates influenza vaccination-induced B-cell response Experimental Hematology, 43 (6). pp. 439-447.

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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.

Item Type: Article
Subjects : Biosciences and Medicine
Authors :
AuthorsEmailORCID
Tete, SMUNSPECIFIEDUNSPECIFIED
Kipling, DUNSPECIFIEDUNSPECIFIED
Westra, JUNSPECIFIEDUNSPECIFIED
de Haan, AUNSPECIFIEDUNSPECIFIED
Bijl, MUNSPECIFIEDUNSPECIFIED
Dunn-Walters, DUNSPECIFIEDUNSPECIFIED
Sahota, SSUNSPECIFIEDUNSPECIFIED
Bos, NAUNSPECIFIEDUNSPECIFIED
Date : 18 March 2015
Identification Number : 10.1016/j.exphem.2015.02.005
Copyright Disclaimer : Copyright 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc.
Depositing User : Symplectic Elements
Date Deposited : 06 Jul 2016 11:41
Last Modified : 06 Jul 2016 11:41
URI: http://epubs.surrey.ac.uk/id/eprint/811123

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