Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall 4EF
Background: Xenoreactive antibodies play an important role in xenograft rejection. Intravenous immunoglobulin (IVIG), which has anti-complement activity and contains anti-idiotypic antibodies, is widely used for the treatment/prevention of antibody-mediated rejection in clinical allotransplantation. However, it is unknown whether IVIG would be useful for inhibiting rejection in clinical xenotransplantation. The aims of the study were to investigate (i) whether IVIG contains anti-pig (especially anti-nonGal) antibodies, and (ii) whether IVIG can attenuate human serum antibody binding to pig cells in vitro.
Methods: (1) Undiluted pooled human serum (HS) and IVIG (40mg/ml, Gammagard, Baxter, Westlake, CA) binding to RBCs from wild-type (WT), GTKO and GTKO/CMAHKO (DKO) pigs (p) was measured by flow cytometry. (2) Inhibition of HS IgG antibody binding to pRBCs by IVIG was assessed by flow cytometry. Binding intensity was presented as relative geometric mean (rGM) (a score of <1.1 being considered negative).
Results: Pooled HS included anti-pig IgG that bound to WT and GTKO pRBCs, but not to DKO pRBCs (Table). IVIG included anti-pig IgG that bound to all of the pRBCs tested, but binding of IVIG was significantly reduced to RBCs from knockout gene pigs. Binding of IVIG to GTKO pRBCs was significantly lower than that of HS (A vs B). IVIG significantly attenuated HS IgG binding to GTKO pRBCs (A vs C).
|A||B||C||A vs B||A vs C||B vs C|
|pRBCs||HS (rGM)||p-Value||IVIG (rGM)||p-Value||HS +IVIG (rGM)||p-Value||p-Value||p-Value|
|GTKO||4.34+/-0.74||<0.01 (vs WT)||2.06+/-0.12||<0.01(vs WT)||2.23+/-0.10||<0.05||<0.05||NS|
|DKO||No binding (<1.1)||<0.01 (vs WT) <0.01(vs GTKO)||1.23+/-0.02||<0.01(vs WT)<0.01(vs GTKO)||No binding (<1.1)||–||–||–|
Conclusions The attenuation of HS antibody binding to pRBCs afforded by IVIG suggests that IVIG administration to recipients of pig grafts might be a treatment option for antibody-mediated rejection after xenotransplantation.
CITATION INFORMATION: Yamamoto T., Li Q., Iwase H., Ayares D., Cooper D., Hara H. The Effect of Intravenous Immunoglobulin on In Vitro Human Antibody Binding to Genetically-Engineered Pig Cells – Relevance to Clinical Xenotransplantation – Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Yamamoto T, Li Q, Iwase H, Ayares D, Cooper D, Hara H. The Effect of Intravenous Immunoglobulin on In Vitro Human Antibody Binding to Genetically-Engineered Pig Cells – Relevance to Clinical Xenotransplantation – [abstract]. https://atcmeetingabstracts.com/abstract/the-effect-of-intravenous-immunoglobulin-on-in-vitro-human-antibody-binding-to-genetically-engineered-pig-cells-relevance-to-clinical-xenotransplantation/. Accessed August 15, 2020.
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