Serum Bactericidal Antibody Responses to Meningococcal Polysaccharide Vaccination as a Basis for Clinical Classification of Common Variable Immunodeficiency

Abstract

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders characterized by hypogammaglobulinemia and increased susceptibility to recurrent pyogenic infections. This study was performed to subclassify CVID on the basis of the bactericidal antibody responses of patients to polysaccharide meningococcal vaccine. Twenty-five patients with CVID (18 male and 7 female) and 25 healthy volunteers received meningococcal polysaccharide vaccine A ؉ C. Serum bactericidal antibody (SBA) titers were measured at baseline and after 3 weeks. Response was correlated with clinical and immunological manifestations of CVID. Twenty-four (96%) of the 25 normal controls had a protective SBA titer of >8 postvaccination, whereas only 16 (64%) of the 25 CVID patients had a protective titer (P value ‫؍‬ 0.013). Among the patients with CVID who were nonresponders, there were significantly increased rates of bronchiectasis (P ‫؍‬ 0.008), splenomegaly (P ‫؍‬ 0.016), and autoimmunity (P ‫؍‬ 0.034) in comparison with patients who had protective SBA titers. A reversed CD4/CD8 ratio was more common in the nonresponder group of patients (P ‫؍‬ 0.053). We conclude that individuals with CVID who cannot produce protective postvaccination titers after receiving meningococcal polysaccharide vaccine are more likely to exhibit bronchiectasis, splenomegaly, and autoimmune diseases. Vaccination response may define subgroups of patients with CVID, enabling more effective monitoring and therapeutic strategies.Common variable immunodeficiency (CVID) is the most common symptomatic antibody deficiency and is characterized by hypogammaglobulinemia in the absence of any recognized genetic abnormality (8,13,21). CVID patients are susceptible to recurrent pyogenic infections (1, 8), as well as autoimmune and neoplastic diseases (6,17). Although infections of the respiratory and gastrointestinal tracts are common, some patients may present with meningitis (1, 8). Encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis are the most prominent pathogens in CVID patients (13,26).Despite attempts during recent decades to identify the underlying immune system defects in CVID, the pathogenesis of CVID remains unknown (26). Thus, the diagnosis of CVID is based on the genetic exclusion of other hypogammaglobulinemias that are well defined at the molecular level (11). Although the underlying pathophysiology of CVID is not clearly understood, a few general defects that lead to alteration of serum immunoglobulin concentrations have been described. Patients with CVID have a defect in B-cell differentiation that leads to impaired secretion of immunoglobulins. Additionally, several abnormalities of T cells have been reported in some patients (26).It has recently been shown that patients with CVID with loss of immunoglobulin M (IgM) memory B cells are susceptible to earlier onset of recurrent infections and more severe complications (5) than those with mild to moderate clinical manifestations. A number of other i...

Common variable immunodeficiency: a heterogeneous group needs further subclassification

“…There are some recent findings that could characterize a group of CVID patients, including abnormalities in regulatory T cells [31][32][33], lymphocyte radiosensitivity [34] and functional antibody response to vaccine antigens [24,35]. Although these abnormalities are not sufficient for the universal classification of CVID, they can pave the way for the discovery of more genetic changes underlying the disease.…”

Background Paper for the update of meningococcal vaccination recommendations in Germany: use of the serogroup B vaccine in persons at increased risk for meningococcal disease

“…However, there appear to be subgroups of patients capable of at least transiently generating adequate antibody responses to the antigens of polysaccharide or protein-based vaccines [107][108][109][110]. Due to the high degree of uncertainty surrounding the degree of IMD risk of IMD, the NNV was not estimated for this patient group.…”

Evaluation of the immunogenic property of NT H. influenzae protein D with Neisseria meningitidis OMV in BALB/c

“…In this study, SBA was performed using pooled serum specimens collected at weeks 0 and 6, and all sera were heat-inactivated for 30 minutes at 56°C. Ten percent (v/v) baby rabbit complement was used as an exogenous complement source [20][21][22]. Sterile 96-well flat-bottom plates were used for the microbactericidal assay.…”