Defects in CD27+ memory B cells and CCR4+ T cells occurring in association with elevated serum Epstein-Barr virus (EBV) loads in XLP patients surviving primary EBV infection

Abstract

Rationale Detailed longitudinal studies of X-linked lymphoproliferative disease (XLP) affected individuals may help to understand the immunological defects that lead patients surviving primary EBV infection to hypogammaglobulinemia. Methods In this report we describe the progressive changes observed in immunoglobulin concentrations, lymphocyte subsets and Epstein Barr virus (EBV) viral load in a newly infected healthy carrier (patient #9) over a two year period. We compare these findings with those observed in his brother (patient #4), 35 years after the starting of his disease. Results IgG, IgM and IgA concentration increased in patient #9 during active infection, but starting one month after, decreased steadily to hypogammaglobulinemia, 5 months later. CD19+ B lymphocytes remained below 3% with a contraction of the B cell memory compartment, CD27+CD19+/CD19, to 20% (Normal: 32%-56%) in both patients. T lymphocyte subpopulations showed a persistent CD4+ cell reduction and a permanent CD8+ T cell expansion. CXCR3+ memory CD4+Th1 cells were expanded and CD4+CCR4+ Th2 lymphocytes were very low in both patients. Both patients had a permanently increased EBV viral load. Conclusions Hypogammaglobulinemia in XLP patients is associated to low total and memory B cell numbers and low Th2 lymphocyte number. Despite an expanded CD3+CD8+ lymphocyte compartment, EBV viral load remains high, without overt clinical symptoms of mononucleosis and no evidence of a lymphoproliferative disease.