The Study of the Terminal Steps of B cell Differentiation Established 3 Subgroups in Pediatric Common Variable Immunodeficiency (CVID) Patients

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

Santiago de Chile

Congreso; III Meeting of The Latin American Society for Primary Immunodeficiencies; 2013

The hypogammaglobulinemia characterizes the heterogeneous group ofprimary immunodeficiency known as CVID. The plasma level of IgG haslow predictive value for the severity of the disease. The study of themechanisms of late B cell differentiation (Class switch recombination(CSR) and Somatic Hypermutation (SHM)) responsible for maturation inanti-corporeal response, could help in the identification of novel geneticdefects.In a previous work we studied the in vivo ability to perform SHM inCVID patients and observed a severe alteration which correlated with alow percentage of circulating ?switched memory? B cells and the presenceof clinical complications (splenomegaly/autoimmunity).The aim of this study was to analyze the change of Ig isotype (CSR) fromCmu to Calpha through the evaluation of DNA repair switch (S) junctionsstructure quality, aberrant in several S-S recombination defects. We clonedand sequenced 194 S-S fragments from 20 CVID pediatric patients and 53fragments from 10 healthy controls. All the switch fragment sequenceswere unique and therefore represented independent CSR events.Our results showed a significant increase in the extent of donor-acceptorhomology on Smu-Salpha joints in CVID patients with respect to thehealthy controls (mean perfect sequence homology 6.9±5.3 bp in CVIDpatients vs 2.3±3.5 bp in healthy controls, P