Late‐Onset Combined Immune Deficiency: A Subset of Common Variable Immunodeficiency with Severe T Cell Defect

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 < 200×106cells/L, and were compared with the remaining 285 patients with CVID. The patients with LOCID more frequently belonged to consanguineous families (29% vs 8%; P=.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 (158×106vs 604×106cells/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; P=.001). The CD19+B cell compartment was also significantly decreased (20×106vs 102×106cells/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

Infections in 252 patients with common variable immunodeficiency.

International audienceBACKGROUND: Common variable immunodeficiency is characterized by recurrent infections and defective immunoglobulin production. METHODS: The DEFI French national study prospectively enrolled adult patients with primary hypogammaglobulinemia. Clinical events before inclusion were retrospectively analyzed at that time. RESULTS: From April 2004 through April 2007, 341 patients were enrolled, 252 of whom had received a diagnosis of common variable immunodeficiency; of those, 110 were male, 142 were female, and 228 were white. The median age at first symptoms was 19 years. The median age at common variable immunodeficiency diagnosis was 33.9 years. The median delay for diagnosis was 15.6 years for the 138 patients with initial symptoms before 1990 and 2.9 years for the 114 patients with initial symptoms from 1990 to the time of the study. The most frequent initial symptoms were upper respiratory tract infections: bronchitis (in 38% of patients), sinusitis (36%), pneumonia (31%), and/or bronchiectasis (14%). Overall, 240 patients had respiratory symptoms. Pneumonia was reported in 147 patients; Streptococcus pneumoniae and Haemophilus influenzae were documented in 46 and 17 cases, respectively. Recurrent or chronic diarrhea was reported in 118 patients. Giardia (35 cases), Salmonella (19), and Campylobacter (19) infections were more frequent in patients with undetectable serum immunoglobulin A (P<.001). Sixteen patients developed opportunistic infections. Persistent infections and requirement for antibiotics despite immunoglobulin substitution correlated with severe defect of memory switched B cells (P=.003) but not with immunoglobulin G trough levels (P=.55). CONCLUSION: Although reduced within the past decade, the delay of diagnosis of common variable immunodeficiency remains unacceptable. Recurrence of upper respiratory tract infection or pneumonia should lead to systematic evaluation of serum immunoglobulin