Splenectomized Patients Have Reduced CD27+ Memory B Cells but Protective Antibody Responses to Pneumococcal Vaccination.

Abstract

Introduction: Splenectomized patients are thought to have poor antibody responses to polyvalent non-conjugate pneumococcal vaccination. Recent studies found that these patients have decreased circulating CD27+ (memory) B cells, suggesting the possibility of a specific defect in splenectomized patients' humoral immunity. In this study we sought to verify this reduction and ascertain whether it correlates with inadequate antibody production. Thus, we enumerated peripheral blood CD27+ B cells in splenectomized patients and non-splenectomized controls, administered a polyvalent non-conjugate pneumococcal vaccine, and compared their IgG antibody titers to all 23 serotypes before and 4 to 6 weeks after immunization.Participants: 31 participants were enrolled: 21 splenectomized patients (6 male, 15 female; age: 10–80 years, mean: 47.3) and 10 non-splenectomized controls (2 male, 8 female; age: 26–64 years, mean: 37.5). Indications for splenectomy included ITP (17), spherocytosis (2), hemolytic anemia (1), and thrombocytopenia-absent radii syndrome (1). No patients received pneumococcal vaccination within 2 years, or IVIG, Rituxan or immunosuppressive therapy within 6 months of enrollment. Time since splenectomy ranged from 6 months to 50 years (mean: 12.5). 17 patients received at least one prior pneumococcal immunization, from 3 to 22 years previously (mean: 8.0). No controls formerly received a pneumococcal vaccination.Results:B Cell Enumeration: Compared to the 10 controls, the 21 splenectomized patients had a greater percentage of circulating B cells (patients: 12.05% ± 7.61; controls: 7.99% ± 2.92; ρ = 0.042), but a significantly reduced CD27+ B cell component (patients: 12.38% ± 8.48; controls: 40.46% ± 18.68; ρ = 0.001). This reduction was not specific to either of the CD27+ B cell populations (IgM+IgD+CD27+: patients: 31.64% ± 19.72; controls: 44.58% ± 16.01; ρ = 0.081. IgM−IgD−CD27+: patients: 52.05 ± 23.71; controls: 48.08% ± 13.89; ρ = 0.628.)Antibody Analysis: Antibody responses to pneumococcal vaccination did not differ significantly between splenectomized patients and non-splenectomized controls. 9 of 13 splenectomized patients and 9 of 10 controls achieved protection to immunization (χ2 = 1.433; ρ = 0.339), defined as a post-vaccination IgG titer ≥ 1.3 μg/ml or a post:pre-vaccination titer ratio ≥ 4, in at least 70% of the serotypes tested (~16 of 23 serotypes). When comparing the mean number of serotypes to which each cohort achieved protection, splenectomized patients and controls mounted statistically similar responses, at 17 and 20 serotypes, respectively (ρ = 0.134). Furthermore, the geometric means of each cohort's post-vaccination IgG titers did not differ significantly in 22 of the 23 serotypes.Conclusion: Splenectomized patients had a significant reduction in their circulating CD27+ B cells. This decrease did not correlate with an impaired antibody response to (re-)immunization with a polyvalent non-conjugate pneumococcal vaccine however, as splenectomized patients and non-splenectomized controls achieved comparable protection and produced similar IgG responses to vaccination. For ITP patients and others who have undergone splenectomy, our data indicates that a pneumococcal vaccine can be effectively administered after splenectomy, if needed.