title: Intravenous Immunoglobulin and Immunomodulation of B-Cell - in vitro and in vivo Effects.
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 CD21(low) 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.
authors: Department of Clinical Medicine, Sapienza University of Rome , Rome , Italy.
authors: Milica
authors: M
authors: Mitrevski
authors: Department of Clinical Medicine, Sapienza University of Rome , Rome , Italy.
authors: Ramona
authors: R
authors: Marrapodi
authors: Department of Clinical Medicine, Sapienza University of Rome , Rome , Italy.
authors: Alessandro
authors: A
authors: Camponeschi
authors: Department of Molecular Medicine, Sapienza University of Rome , Rome , Italy.
authors: Filomena Monica
authors: FM
authors: Cavaliere
authors: Department of Clinical Medicine, Sapienza University of Rome , Rome , Italy.
authors: Cristina
authors: C
authors: Lazzeri
authors: Department of Clinical Medicine, Sapienza University of Rome , Rome , Italy.
authors: Laura
authors: L
authors: Todi
authors: Department of Clinical Medicine, Sapienza University of Rome , Rome , Italy.
authors: Marcella
authors: M
authors: Visentini
keywords: B lymphocytes; CD21low B-cell; autoimmune disease; immunomodulation; intravenous immunoglobulin
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