In vitro comparison of the complement‐scavenging capacity of different intravenous immunoglobulin preparations

Abstract

In vitro analysis allows comparison of the complement-inhibitory properties of IVIG preparations. The extent of complement scavenging varies between the products.

A fully recombinant human IgG1 Fc multimer (GL-2045) inhibits complement-mediated cytotoxicity and induces iC3b

“…These findings are in keeping with prior studies, demonstrating that IVIG blocks complement activation through covalent interactions with C4b 32 and C3b, 24,25 sequestering them from both the amplification loop and surface of opsonized cells 33 and preventing local MAC activation. [34][35][36][37][38][39][40] Despite differences in their ability to directly inhibit the alternative form of C3 convertase, both GL-2045 and IVIG indirectly govern the alternative form of C3 convertase by potentiating factor H activity through mechanisms still to be determined. These data are consistent with prior reports demonstrating that IVIG modulates C3bBb cleavage by factor H. 33 Similarly, pentraxin-3, an antibodylike protein, can both bind and sequester C1q and potentiate factor H function, allowing apoptotic cells to die a "silent death."…”

Polyclonal immunoglobulin G for autoimmune demyelinating nervous system disorders

“…In the final product, IgG antibodies of all four subclasses comprise 95-98% of the total protein, depending on the commercial preparation. Both the reactivity to individual antigens and the IgG effector functions, as described below, may vary among preparations as well as from batch to batch and are influenced by different donor pools and manufacturing processes [4,5]. In addition to their main components, commercial IgG preparations contain small quantities of IgA, which are responsible for allergic reactions in persons with selective IgA deficiency and anti-IgA antibodies, as well as traces of IgM, soluble CD4, CD8, HLA molecules, and cytokines [6].…”

Advances in pharmacotherapy to treat kidney transplant rejection

“…Anti-thymocyte globulins/ anti-lymphocyte globulins Effect on T-cells: ADCC, CDC, opsonisation, AICD [135][136][137][138][139] Effect on B-cells: inhibition of B-T cooperation, B-cell lysis and apoptosis [129,140] Down-regulation of leucocyte adhesion [141,142] No effect on bone marrow and spleen plasma cells [129,140] Anti-CD52 monoclonal antibody Alemtuzumab ADCC, AICD, prolonged T-cell lymphopenia, expansion of Tregs [161] Anti-IL-2 receptor monoclonal antibodies Basiliximab, Daclizumab T-cell activation blockade and apoptosis [144] Polyclonal immunoglobulins -Antigen neutralisation [182][183][184][185] Down regulation of immune responses, AICD and inhibition of MAC formation [186][187][188] Anti-CD20 monoclonal antibodies Rituximab B-cell: ADCC, CDC, apoptosis [207,208] Anti-C5 Eculizumab High affinity for C5, blocking C5 cleavage, thereby preventing the generation of complement components C5a and C5b-9 and formation of the MAC [215] ADCC: Antibody-dependent cell cytotoxicity; AICD: Activation-induced cell death; CDC: Complement-dependent cytotoxicity; MAC: Membrane attack complex. Controversial data [132,133] Dose scheme to address Prospective data needed Anti-thymocyte globulins No beneficial effect vs. corticosteroids [149][150][151][152] Rescue therapy according to benefice-risk balance [154][155][156][157][158] --Consider when TCMR-associated lesions [160] Increase in infection and cardiovascular-related death alone [154,155] Increase in infection related death in association with Rituximab [160] Alemtuzumab Lower patient survival with higher infection risk [165] Lower pati...…”