Intravenous immunoglobulin replacement therapy in the treatment of patients with common variable immunodeficiency...

Common variable immunodeficiency (CVID) is characterized by humoral immunodeficiency resulting in increased susceptibility to infections and diminished responses to protein and polysaccharide vaccines. Intravenous immunoglobulins (IVIgs) constitute a replacement therapeutic regimen for CVID and other primary and selected secondary immunodeficiencies but their mode of action is still not fully understood.

The purpose of this study was to assess the effect of IVIg replacement therapy on the population of regulatory T cells (cells expressing CD4, CD25 and low levels of CD127) [T(regs)]), plasma levels of interleukin (IL)-2 and IL-10, and expression of fragment, crystallizable γ receptor IIb (Fc γ RIIb) [CD32b] on CD19+ B cells in CVID patients.

This was an open-label prospective trial that included 17 CVID patients and seven healthy subjects as case controls. The diagnosis of CVID was primarily established by clinical criteria designed by the European Society for Immunodeficiencies (ESID) and was confirmed by low serum levels of two out of three subclasses of immunoglobulins (IgG, IgA or IgM). All CVID patients were treated with the IVIg preparation Flebogamma® 5%, a highly purified, pasteurized normal human IgG extracted from the serum of healthy individuals, administered at a dose of 300 mg/kg by slow 2-hour intravenous infusion. Blood samples were collected 30 minutes before the infusion and 30 minutes and 2 weeks after the termination of the infusion. We examined: (i) the plasma levels of IL-2 and IL-10; (ii) the percentage of CD4+ T cells and T(regs); and (iii) the expression of Fc γ RIIb on the surface of CD19+ B cells.

CVID patients had higher plasma levels of IL-2 (p = 0.045) and IL-10 (p = 0.002) as well as a higher expression of Fc γ RIIb on CD19+ B cells (p =  0.0119) before IVIg compared with healthy controls. The infusion of IVIg led to further increases in the plasma levels of these cytokines 30 minutes after the termination of the infusion versus baseline (IL-2: p =  0.0004; IL-10: p = 0.0003). IVIg did not affect the expression of Fc γ RIIb. Finally, IVIg infusion resulted in elevation of the percentages of CD4+ T cells (p = 0.028) and T(regs) (p = 0.006) in the blood 30 minutes after the infusion.

Flebogamma® 5% as replacement therapy not only supplies immunoglobulins but also modulates the immune response, and in this way may provide additional benefits to patients with CVID.