Long-term follow-up on affinity maturation and memory B-cell generation in adult patients with common variable immunodeficiency

Introduction: Common variable immunodeficiency (CVID) comprises a heterogeneous group of primary immunodeficiency disorders, and diagnostic delay is a well-known problem. In the EUROclass classification prognostic outcome is predicted by immunophenotyping of B-lymphocyte subsets. Levels of somatic hypermutation (SHM) have been associated with recurrent respiratory tract infections. Aim: To investigate stability of B-lymphocyte subpopulations and SHM in CVID patients during a long follow-up period. Methods: In a cohort of 33 CVID patients, SHM was measured in kappa light-chain transcripts, and memory B-cell subsets were studied using flow cytometry in an average period of 8.8 years (range 3-19). Results: During the follow-up period, severely reduced proportions of switched memory B-cells (< 2% of Bcells) were found in 60% of the patients, but only half remained stable during the period. Fluctuations around the 2% cutoff were frequent. Switched memory B-cells below the normal range (< 5% of B-cells) were detected in 67% of the patients at inclusion, and remained reduced in the majority during follow-up. At inclusion 73% of the patients had reduced levels of SHM, and in the majority levels remained reduced. Conclusion: Memory B-cell subsets and levels of SHM were not consistently stable parameters. In our study, the EUROclass cutoff for switched memory B-cells < 2% was not a constant classification parameter during a long follow-up period, whereas a cutoff < 5% provided more consistent results.