Non infectious complications in pediatric-onset CVID patients correlate with defects in somatic hypermutation and class switch recombination

ALMEJÚN MARÍA BELÉN; CAMPOS BÁRBARA; GALLICCHIO MIGUEL; ZELAZKO MARTA; OLEASTRO MATÍAS; OPPEZZO PABLO; DANIELIAN SILVIA

CABA

Congreso; I Meeting LASID, FAIC, SAI 2015; 2015

Background: Common variable immunodeficiency is a heterogeneous syndrome characterized by impaired immunoglobulin production and usually presented with a normal number of peripheral B cells. Most attempts aiming to classify these patients have mainly been focused on T cell phenotypes or B cell phenotypes and their ability to produce protective antibodies, but it is still a major challenge to find a suitable classification that includes the clinical and immunological heterogeneity of these patients.Objective: In this work, we evaluated the late stages of B cell differentiation in a heterogeneous population of pediatric-onset CVID patients in order to assess their ability to perform somatic hypermutation and/or class switch recombination.Methods: We performed a previously reported assay, IgκREHMA, to evaluate the in vivo somatic hypermutation status. To investigate the quality of the double strand break repairs in class switch recombination process in vivo we amplified switch regions from genomic DNA. We also tested the ability to generate immunoglobulin germline and circle transcripts and to upregulate activation-induced cytidine deaminase gene through in vitro T-dependent and T-independent stimuli.Results: Our results showed that almost all patients (24/25) had -to a greater or lesser extent- an altered somatic hypermutation. Eighty percent of patients presented an increased microhomology usage at switch regions. In vitro activation revealed that CVID patients behaved heterogeneously in terms of responsiveness to T-dependent stimuli.Conclusion: Our CVID cohort can be gathering in three groups of whom the first, lacking optimal somatic hypermutation and class switch recombination, accumulated the noninfectious clinical complications.