Late-onset combined immune deficiency: A subset of common variable immunodeficiency with severe T cell defect

Abstract

Background: Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic infections (OIs). Methods: The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs. Results: Among 313 patients with CVID, 28 patients (8.9%) presented with late-onset combined immune deficiency (LOCID), defined by the occurrence of an OI and/or a CD4+ T cell count <200×106 cells/L, and were compared with the remaining 285 patients with CVID. The patients with LOCID more frequently belonged to consanguineous families (29% vs 8%; Pp.004). They differed from patients with CVID with a higher prevalence of splenomegaly (64% vs 31%), granuloma (43% vs 10%), gastrointestinal disease (75% vs 42%), and lymphoma (29% vs 4%). Even on immunoglobulin substitution, they required more frequent antibiotics administration and hospitalization. Lymphocyte counts were lower, with a marked decrease in CD4+ T cell counts (158×106 vs 604×10 6 cells/L; P < .001) and a severe defect in naive CD45RA +CCR7+CD4+ T cell counts (<20% of total CD4+ T cells in 71% of patients with LOCID vs 37% of patients with CVID; Pp.001). The CD19+ B cell compartment was also significantly decreased (20×106 vs 102×106 cells/L; P < .001). Conclusions: LOCID differs from classic CVID in its clinical and immunologic characteristics. Systematic T cell phenotype may help to discriminate such patients from those with CVID. Identification of this phenotype should result in a more fitted diagnostic and therapeutic approach of infections and could provide insights for genetic diagnosis. © 2009 by the Infectious Diseases Society of America. All rights reserved.