title: Intravenous IgG (IVIG) and subcutaneous IgG (SCIG) preparations have comparable inhibitory effect on T cell activation, which is not dependent on IgG sialylation, monocytes or B cells.
abstract: IVIG modulates T cell activation in vitro and inflammatory-autoimmune conditions in vivo. Sialylation of IgG, Fc receptor interactions, modulation of monocyte/macrophage/B cell functions have been implicated in IVIG effects. Subcutaneous IgG (SCIG) therapy is increasingly used for IgG replacement but whether these preparations share the effects of IVIG on T cell modulation is not documented. We compared the potency of SCIG-Hizentra™ (20% IgG preparation) with IVIG-Privigen® (10% IgG) for T cell inhibition, and assessed the involvement of IgG sialylation, monocytes and B cells in this process. Human PBMCs or sorted cells were cultured 3-7 days, and T cells were stimulated with immobilized anti-CD3 mAb or Candida antigen. Thymidine incorporation into DNA was quantitated and cytokines assayed by ELISA/Luminex® assay. IVIG and SCIG both dose-dependently (1-20mg/ml) inhibited (up to >80%) T cell proliferation to anti-CD3 mAb. Response to Candida albicans was comparably inhibited by IVIG and SCIG by 50-80% at 10mg/ml with inhibition even at 3mg/ml (P<0.05). These effects were not affected by depletion of sialic acid containing IgG using neuraminidase treatment or lectin affinity chromatography. With anti-CD3 or Candida stimulation, IL-1β, IL-2, IL-5, IL-6, IL-13, GMCSF, TNF-α, interferon-γ (with anti-CD3) and IL-17 (with Candida) levels were suppressed by IVIG or SCIG, with no effect on IL-4, IL-10, IL-12, IL-15 or TGFβ. Monocytes or B cells were not required for IgG-induced suppression of proliferation, in fact depletion of monocytes potentiated the IgG-induced inhibition. Reconstitution with monocytes restored the original inhibitory effect. These data show that IVIG (Privigen®) and SCIG (Hizentra™) have comparable inhibitory effects on T cell activation, which do not require sialylation of IgG. Inhibition is independent of monocytes or B cells. There is a potent suppression of multiple effector cytokines. Like IVIG, SCIG therapy is expected to show immunomodulatory activity.
authors.affiliation: Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada; Department of Pathology, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada. Electronic address: andrew.issekutz@iwk.nshealth.ca.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Issekutz
authors.affiliation: Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada; Department of Pathology, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada.
authors.forename: Derek
authors.initials: D
authors.lastname: Rowter
authors.affiliation: CSL Behring, Bern, Switzerland.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Miescher
authors.affiliation: CSL Behring, Bern, Switzerland. Electronic address: Fabian.Kaesermann@cslbehring.com.
authors.forename: Fabian
authors.initials: F
authors.lastname: Käsermann
mesh_terms: D000946:Antigens, Fungal / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002176:Candida albicans / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D055104:Infusions, Subcutaneous; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D019158:N-Acetylneuraminic Acid; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D000946:Antigens, Fungal; D017252:CD3 Complex; D016207:Cytokines; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D019158:N-Acetylneuraminic Acid
keywords: Cytokine; Immunomodulation; Lymphocyte; Proliferation; Sialyl IgG