Predictive Markers for Humoral Influenza Vaccine Response in Patients with Common Variable Immunodeficiency

Background: A subgroup of patients with common variable immunodeficiencies (CVIDs) responds to vaccination. The aim of this study was to try to identify predictive markers for those with a humoral immune response after influenza vaccination.

Methods: Forty-eight patients with CVID (29 female and 19 male patients; mean age, 57.7 years) were vaccinated with the A(H1N1) influenza vaccine Pandemrix (GlaxoSmithKline, Wavre, Belgium) and boosted after 1 month. Blood samples were collected before each vaccination and 2 months later. Patients with a 4-fold titer increase in results on the hemagglutinin inhibition test (≥1:40) were considered responders and compared with nonresponders for clinical, immunologic, and genetic markers.

Results: Eight (16.7%) patients responded to the vaccination. A significantly higher proportion of the responders, who showed a EUROclass SmBTr21 profile (P = .03) with a post-germinal center B-cell pattern (P = .04) in blood, experienced enteropathies (P = .04) compared with nonresponders. On the other hand, bronchiectasis was found exclusively among nonresponders (n = 7), as was autoimmune cytopenia (n = 5). Nonresponders with a EUROclass SmBTr21 profile (P = .02) had a significantly greater prevalence of progressive antibody deficiency (P = .048) and, at diagnosis, a higher mean serum IgM level (P = .03), lower mean serum IgG level (P = .007), expansion of absolute counts of cytotoxic CD8 T cells (P = .033), and increased proportion of memory CD8 T cells (P = .044) in blood. CVID-associated HLA markers were not detected in responders (P = .03).

Conclusion: About one fifth of the patients with CVIDs achieved protective antibody levels after A(H1N1) vaccination and selected clinical, and immunologic markers were identified that might predict a positive outcome of influenza vaccination. Patients with CVID should be offered vaccination also against seasonal influenza because of the potential severity of the infection and risk for bacterial complications.