The Effect of Intravenous Immunoglobulin on Human Complement-Dependent Cytotoxicity of Pig Cells: Benefit? Or Harm?
1Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, 2Revivicor, Blacksburg, VA
Meeting: 2019 American Transplant Congress
Abstract number: D86
Keywords: Immunoglobulins (Ig), Pig, Xenoreactive antibodies
Session Information
Session Name: Poster Session D: Xenotransplantation
Session Type: Poster Session
Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Xenoreactive antibodies and complement play an important role in pig xenograft rejection. Intravenous immunoglobulin (IVIG) is widely used in desensitization protocols and for the treatment/prevention of antibody-mediated rejection in allotransplantation. However, it is unknown whether IVIG would be useful for inhibiting rejection in xenotransplantation. The aims of the study were to investigate (i) whether IVIG contains anti-pig antibodies, (ii) whether IVIG can attenuate human serum antibody binding to pig cells in vitro, and (iii) whether IVIG can inhibit the cytotoxicity of human serum to pig cells in vitro.
*Methods: (1) Undiluted pooled human serum (HS) and five different commercial preparations of IVIG were tested for IgM and IgG binding to red blood cells (RBCs) from wild-type (WT), GTKO, and GTKO/CMAHKO/β4GalNT2KO (TKO) pigs by flow cytometry. (2) Inhibition of HS IgM and IgG antibody binding by IVIG to pRBCs and pig aortic endothelial cells (pAECs) was measured by flow cytometry. (3) Complement-dependent lysis of pRBCs was measured by hemolytic assay, and cytotoxicity of pAECs by a complement-dependent cytotoxicity assay.
*Results: (1) Pooled HS contained IgM/IgG that bound to WT and GTKO pRBCs, but not to TKO pRBCs. (2) All of the IVIGs tested also contained IgM/IgG that bound to WT and GTKO pRBCs, but not to TKO pRBCs (except one brand that bound to TKO pRBCs). (3) IgM and IgG binding of IVIG (Flebogamma, Gammagard or Octagam) to WT pRBCs was significantly less than binding of HS (p<0.05). (4) IgM and IgG binding of HS to pRBCs was not significantly reduced by the addition of IVIG. (5) The cytotoxicity of HS against GTKO pRBCs (which was 100%) was reduced to 7% by the addition of high-dose IVIG (p<0.01), and the cytotoxicity of HS to WT and GTKO pAECs (75% and 13%, respectively) was inhibited by high-dose IVIG to 20% and 0%, respectively (both p<0.01).
*Conclusions: (i) Neither HS nor IVIG contained IgM/IgG that bound to TKO pig cells. (ii) The administration of IVIG to recipients of pig grafts might reduce antibody-mediated rejection. (iii) This effect is induced by inhibition of complement, but not by reduced IgM or IgG binding to the pig cells.
To cite this abstract in AMA style:
Yamamoto T, Li Q, Banks A, Iwase H, Ayares D, Cooper DK, Hara H. The Effect of Intravenous Immunoglobulin on Human Complement-Dependent Cytotoxicity of Pig Cells: Benefit? Or Harm? [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/the-effect-of-intravenous-immunoglobulin-on-human-complement-dependent-cytotoxicity-of-pig-cells-benefit-or-harm/. Accessed June 1, 2025.« Back to 2019 American Transplant Congress