Abstract
Intravenous immunoglobulin (IVIG) is used as replacement therapy in patients with antibody deficiencies and at higher dosages in immune-mediated disorders. Although different mechanisms have been described in vitro, the in vivo immunomodulatory effects of IVIG are poorly understood. Different studies have suggested that IVIG modulates B-cell functions as activation, proliferation, and apoptosis. Recently, it was shown that IVIG induces in vitro B-cell unresponsiveness similar to anergy. In accord with this, we recently reported that IVIG therapy in patients affected by common variable immunodeficiency (CVID) interferes in vivo with the B-cell receptor (BCR) signaling by increasing constitutive ERK activation and by reducing the phosphorylated ERK increment induced by BCR cross-linking. Moreover, we observed that IVIG induces in CVID patients an increase of circulating CD21low B-cells, an unusual population of anergic-like B-cells prone to apoptosis. Therefore, IVIG at replacement dose in vivo could prime B-cells to an anergic, apoptotic program. Here, we discuss these recent findings, which may improve our understanding of the immunomodulatory effects of IVIG, individualizing single involved molecules for more specific treatments.
Highlights
Used only in primary and secondary immune deficiencies, intravenous immunoglobulin (IVIG), as a safe and efficacious therapy, has increasingly been used for the treatment of different autoimmune and systemic inflammatory diseases [1]
IgG antibodies are important for protecting us from microbial infections, but IgG autoantibodies are major pathogenetic factors in several autoimmune diseases that benefit from IVIG therapy
CD21low B-cells are expanded in a subset of patients with common variable immunodeficiency (CVID) and in some other immunological disorders and are characterized by high-constitutive ERK activation [41], low responsiveness to TLR9 and B-cell receptor (BCR) stimuli [42, 43], and propensity to apoptosis [44]
Summary
Used only in primary and secondary immune deficiencies, intravenous immunoglobulin (IVIG), as a safe and efficacious therapy, has increasingly been used for the treatment of different autoimmune and systemic inflammatory diseases [1]. IVIG AND B-CELL INHIBITORY RECEPTORS BINDING Interaction of the BCR with the antigen results in signal transduction, which leads to the modulation of gene expression, resulting in activation, anergy, or apoptosis of B-cells.
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