title: Fragments of truth: T-cell targets of polyclonal immunoglobulins in autoimmune diseases.
abstract: The expanding therapeutic use of high-dose intravenous immunoglobulin (IVIg) in autoimmune diseases has raised important practical and conceptual issues over the last few years. These have prompted a number of research efforts aimed at characterizing aspects of the mechanism of action of current IVIg preparations, which might lead to the development of standardized, more cost-effective agents. Although polyclonal IgG in these preparations are mostly thought to act via direct interference with disease-specific, pathogenic autoantibodies, evidence from clinical and experimental work points to the involvement of crucial checkpoints upstream of self-reactive B-cell activation and autoantibody production. Reviewed herein are the results of the most recent studies documenting the crucial role of regulatory T cells (Treg) in the immunomodulatory activity of IVIg, and the molecular mechanisms mediating the effect of specific IgG fragments and glycoforms on Treg activity and the ensuing downregulation of T-cell effector responses of different sign and magnitude. Further progress in this area of translational research may lead to the development of innovative strategies aimed at restoring tolerance in autoimmune diseases.
authors.affiliation: University of Salerno, Department of Medicine and Surgery, Via Salvador Allende, 43, I-84081 Baronissi, Salerno, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Petta
authors.affiliation: University of Salerno, Department of Medicine and Surgery, Via Salvador Allende, 43, I-84081 Baronissi, Salerno, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: De Luca
authors.affiliation: University of Salerno, Department of Medicine and Surgery, Via Salvador Allende, 43, I-84081 Baronissi, Salerno, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Triggiani
authors.affiliation: University of Salerno, Department of Medicine and Surgery, Via Salvador Allende, 43, I-84081 Baronissi, Salerno, Italy. Electronic address: vcasolaro@unisa.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Casolaro
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D016756:Immunoglobulins, Intravenous / Q000592:standards / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000592:standards / Q000627:therapeutic use*; D011786:Quality Control; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D058408:Th1-Th2 Balance / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors