Elevated levels of activated CD4 T cells in common variable immunodeficiency: association with clinical findings.

BACKGROUND

Common variable immunodeficiency (CVID) is a very heterogeneous syndrome defined by impaired immunoglobulin production. The primary defect remains unknown, but many reports describe peripheral blood T and B lymphocyte dysfunctions in a substantial proportion of CVID patients. Immunophenotypic alterations on memory B lymphocytes correlate with clinical findings. A B-cell-oriented classification principle of the patients has been proposed.

METHODS AND RESULTS

We investigated the expression of activation surface molecules on CD4 and CD8 T-cells from 14 patients with CVID, 6 non-CVID hypogammaglobulinemic patients with recurrent infections, 47 asymptomatic HIV-positive patients without AIDS defining conditions and 23 healthy subjects. Lymphocyte subsets were analysed by three-colour flow cytometry. Monoclonal panel: CD38-FITC/HLADR-PE/CD4 or CD8-PerCP. In CVID patients serum levels of CD4 T-cells co-expressing the activation marker HLA-DR [CD4+DR+ (34 %), CD4+CD38+DR+ (18 %)] were significantly elevated compared with controls. Significant increases in CD8+DR+ (54%), CD8+ CD38+ (43%) and CD8+CD38+DR+ (29%) T-cells were observed in comparison with healthy controls. CVID patients with splenomegaly, lower pre-infusion IgG levels (< 600 mg/dl), autoimmune or lymphoproliferative conditions demonstrated even higher levels of CD4+CD38+DR+T cells (22, 22, 21 and 21% respectively) compared with other CVID patients (13, 13, 15 and 15% respectively).

CONCLUSION

These findings indicate a state of ongoing T lymphocyte activation which is associated with clinical findings frequently observed in CVID.