In vivo modulation of the expressions of Fas and CD25 by intravenous immunoglobulin in common variable immunodeficiency

Abstract

Although the presence of physiologic anti-CD95 (Fas, APO-1) autoantibodies in intravenous immunoglobulin (IVIG) preparations is known, the effects of these antibodies in patients with common variable immunodeficiency are unclear (CVID). The aim of the study was to assess the effects of IVIG in Fas expression, activation markers and the subsets of T cells in patients with CVID. We studied 15 cases with CVID and 10 healthy controls with no signs of immunodeficiency. The Fas expression of T cells, activation markers (CD25, CD69 and HLA-DR) and T-cell subsets were analyzed by four-color flow cytometry. We found that the Fas expression of CD3+ T cells in patients was significantly higher than in controls. In addition, there was a significant increase in the Fas expression of CD3+ T cells and CD4+ T cells, and the CD25 expression of CD3+ and CD4+ T cells after IVIG supplementation (P < 0.05). The CD69 and HLA-DR expressions of T cells and CD8+ T cells were not affected by IVIG infusion. Our observation showed that IVIG replacement causes an increase in the Fas and CD25 expressions in patients with CVID. These data suggest that the Fas protein may have an important role in the effects of IVIG for the control of autoimmunity in patients with CVID, as well as in the generation of autoimmune disease.

Intravenous immunoglobulin induces proliferation and immunoglobulin synthesis from B cells of patients with common variable immunodeficiency: A mechanism underlying the beneficial effect of IVIg in primary immunodeficiencies

“…Thus, IVIg increases the TNFa and IL-2 in vivo in CVID patients with unchanged IFN-g expression [59]. It was also suggested that IVIg by up-regulating the Fas expression on CD4þT cells, controls autoimmunity in CVID patients [60]. Further, we have previously demonstrated that IVIg rescues defective differentiation of DC from both CVID and X-linked agammaglobulinemia patients with an enhanced production by DC of anti-inflammatory cytokine IL-10 [61,62].…”

Impact of intravenous immunoglobulin on the dopaminergic system and immune response in the acute MPTP mouse model of Parkinson’s disease

“…Interestingly, a significant decrease in CD4 + /CD8 + ratio is observed in PD patients as well [69-71], possibly accounted for by an increased susceptibility to apoptosis observed in CD4 + T cells, consequent of Fas overexpression [72]. IVIg has been reported to modulate the level of expression of Fas and FasL and to inhibit FasL-dependent apoptosis, in both in vivo and in vitro studies [34,73-75]. This action of IVIg on the Fas/FasL pathway could have been translated into neurorestoration.…”

T-Cell Abnormalities in Common Variable Immunodeficiency

“…IVIG reduces expression of the activation markers Ki67, CD38, and HLA-DR on CD8 + T cells [94]. However, Artac et al [96] reported that expression of CD69 and HLA-DR by CD8 + T cells is not affected by IVIG. The immunological mechanisms by which IVIG can normalize T-cell counts and function in CVID patients remains unclear, but Dolcino et al [97] reported that lower expression of LEPR, a major gene in CD4 + T-cell proliferation, returned to normal values after IVIG treatment [97].…”