Effect of intravenous immunoglobulins on in vitro immunoglobulin formation in patients with antibody immunodeficiency.

Seventeen patients with antibody immunodeficiency (9 subclass IgG immunodeficiencies, 8 common variable immunodeficiencies) and clinically unambiguous immunodeficiency symptomatology participated in the study with 14 healthy donors. The patients were given regular intravenous immunoglobulin (IVIG) infusions with Endobulin. Blood was collected before and 7 days after infusion of the usual IVIG dose. Mononuclear cells were isolated from peripheral blood (PBMC) of the patients by Ficoll-Paque gradient centrifugation. In order to monitor the ability to inhibit or activate polyclonal production of immunoglobulins in vitro, we stimulated PBMC with pokeweed mitogen (PWM) and with a mixture of pokeweed mitogen + concanavalin A (PWM+ConA). We found that an immunomodulatory effect of IVIG persists in vitro even one week after infusion. Polyclonally stimulated IgA and IgM production was suppressed by IVIG infusion mainly in patients with IgG subclass deficiency. The positive stimulatory effect of IVIG infusion on IgG production was confirmed. The IgG production increased in vitro after infusion in both groups of patients and was significantly higher than in healthy donors. Co-stimulation of PWM-stimulated cells with ConA caused an inhibition of immunoglobulin release in normal healthy donors. The infusion supported the capability of ConA to inhibit IgG production in vitro in patients with IgG subclass deficiency, whereas an increase in IgG production with PWM+ConA stimulation after infusion was found in CVID patients. We assume that lymphocytes activated by ConA produce suppressive factors, which can be affected by the IVIG infusion and which can have both an immunostimulatory and an immunosuppressive effect.