Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasma cells in the bone marrow, secreting monoclonal (M) paraprotein. MGUS is associated with increased susceptibility to infections, which may reflect altered B-cell repertoire. To investigate this, we examined the IgM, IgG and IgA B-cell repertoire diversity in MGUS at baseline and after influenza vaccination (n=16) in comparison to healthy controls (HCs) (n=16). The CDR3 region of the immunoglobulin heavy chain variable (IGHV) 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 inter-individual 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). Post-vaccination, 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 post-vaccination, 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.
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