Intravenous Immunoglobulins Promote an Expansion of Monocytic Myeloid-Derived Suppressor Cells (MDSC) in CVID Patients

Abstract

Common variable immunodeficiency disorders (CVID), the most common primary immune deficiency, includes heterogeneous syndromes characterized by hypogammaglobulinemia and impaired antibody responses. CVID patients frequently suffer from recurrent infections and inflammatory conditions. Currently, immunoglobulin replacement therapy (IgRT) is the first-line treatment to prevent infections and aminorate immune alterations in CVID patients. Intravenous Immunoglobulin (IVIg), a preparation of highly purified poly-specific IgG, is used for treatment of immunodeficiencies as well as for autoimmune and inflammatory disorders, as IVIg exerts immunoregulatory and anti-inflammatory actions on innate and adaptive immune cells. To determine the mechanism of action of IVIg in CVID in vivo, we determined the effect of IVIg infusion on the transcriptome of peripheral blood mononuclear cells from CVID patients, and found that peripheral blood monocytes are primary targets of IVIg in vivo, and that IVIg triggers the acquisition of an anti-inflammatory gene profile in human monocytes. Moreover, IVIg altered the relative proportions of peripheral blood monocyte subsets and enhanced the proportion of CD14+ cells with a transcriptional, phenotypic, and functional profile that resembles that of monocytic myeloid-derived suppressor cells (MDSC). Therefore, our results indicate that CD14 + MDSC-like cells might contribute to the immunoregulatory effects of IVIg in CVID and other inflammatory disorders.

Intravenous Immunoglobulin: Mechanism of Action in Autoimmune and Inflammatory Conditions

“…IVIG inhibited activation of monocytes and macrophages both in mice and humans, and induced antiinflammatory cytokines like IL-1 receptor antagonist (IL-1RA), TGF-β and IL-10 [36][37][38][39][40][41] . IVIG induced Fas-mediated apoptosis of innate cells and neutralized various innate inflammatory cytokines by virtue of high-affinity anti-cytokine IgG antibodies 42 . IVIG also promoted an expansion of monocytic myeloidderived suppressor cells 43 .…”

Clinical and immunological characterization of IgG subclass deficiency reveals that low levels of pneumococcal antibodies associate with need of immunoglobulin replacement therapy

“…According to present Swedish national guidelines [11], the effect of IgRT should be evaluated after 12-18 months and followed by a discontinuation trial, during which IgRT is reintroduced if clinically signi cant infections reoccur or if there are signs of reduced lung function. It has been suggested that immunoglobulins used in replacement therapies may modulate the immune response [12,13]. Longitudinal prospective studies on the immune-modulatory effects of IgRT in PAD are lacking.…”