Abstract

BackgroundAnnual influenza vaccination is recommended to all individuals over 6 months of age, including predominantly antibody deficiency (PAD) patients. Vaccination responses are typically evaluated by serology, and because PAD patients are by definition impaired in generating IgG and receive immunoglobulin replacement therapy (IgRT), it remains unclear whether they can mount an antigen‐specific response.ObjectiveTo quantify and characterise the antigen‐specific memory B (Bmem) cell compartment in healthy controls and PAD patients following an influenza booster vaccination.MethodsRecombinant hemagglutinin (HA) from the A/Michigan/2015 H1N1 (AM15) strain with an AviTag was generated in a mammalian cell line, and following targeted biotinylation, was tetramerised with BUV395 or BUV737 streptavidin conjugates. Multicolour flow cytometry was applied on blood samples before and 28 days after booster influenza vaccination in 16 healthy controls and five PAD patients with circulating Bmem cells.ResultsRecombinant HA tetramers were specifically recognised by 0.5–1% of B cells in previously vaccinated healthy adults. HA‐specific Bmem cell numbers were significantly increased following booster vaccination and predominantly expressed IgG1. Similarly, PAD patients carried HA‐specific Bmem cells, predominantly expressing IgG1. However, these numbers were lower than in controls and did not increase following booster vaccination.ConclusionWe have successfully identified AM15‐specific Bmem cells in healthy controls and PAD patients. The presence of antigen‐specific Bmem cells could offer an additional diagnostic tool to aid in the clinical diagnosis of PAD. Furthermore, alterations in the number or immunophenotype of HA‐specific Bmem cells post‐booster vaccination could assist in the evaluation of immune responses in individuals receiving IgRT.

Highlights

  • Antibody deficiency (PAD) comprises the largest group of patients (~70%) with a primary immunodeficiency disorder (PID).[1,2,3,4,5] Patients are defined by an impaired antibody (Ab) response to antigen stimulation.[6,7,8] Within the group of predominantly antibody deficiency (PAD) patients, those with a complete absence of serum immunoglobulin (Ig) and of circulating B cells are defined as having agammaglobulinemia

  • Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc

  • While our observations are limited by the small number of patients included in the study, we show that PAD patients had an increased proportion of Bmem cells expressing IgG3, the subclass encoded by the most IGHM-proximal constant gene region

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Summary

Introduction

Antibody deficiency (PAD) comprises the largest group of patients (~70%) with a primary immunodeficiency disorder (PID).[1,2,3,4,5] Patients are defined by an impaired antibody (Ab) response to antigen stimulation.[6,7,8] Within the group of PAD patients, those with a complete absence of serum immunoglobulin (Ig) and of circulating B cells are defined as having agammaglobulinemia. To quantify and characterise the antigen-specific memory B (Bmem) cell compartment in healthy controls and PAD patients following an influenza booster vaccination. HA-specific Bmem cell numbers were significantly increased following booster vaccination and predominantly expressed IgG1. PAD patients carried HAspecific Bmem cells, predominantly expressing IgG1 These numbers were lower than in controls and did not increase following booster vaccination. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc

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