Anti-pig IgE and IgA Antibodies in Naive Primates and Nonhuman Primates With Pig Xenografts.

Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0132144 Publication Model: Print Cited Medium: Internet ISSN: 1534-6080 (Electronic) Linking ISSN: 00411337 NLM ISO Abbreviation: Transplantation Subsets: MEDLINE

Publication: Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: Baltimore, Williams & Wilkins.

Antibodies, Heterophile/*blood ; Erythrocytes/*immunology ; Graft Rejection/*immunology ; Immunoglobulin A/*blood ; Immunoglobulin E/*blood ; Transplantation, Heterologous/*adverse effects; Animals ; Animals, Genetically Modified ; Galactosyltransferases/genetics ; Galactosyltransferases/immunology ; Graft Rejection/blood ; Graft Rejection/pathology ; Humans ; Macaca mulatta ; Mixed Function Oxygenases/genetics ; Mixed Function Oxygenases/immunology ; N-Acetylgalactosaminyltransferases/genetics ; N-Acetylgalactosaminyltransferases/immunology ; Papio ; Species Specificity ; Sus scrofa/genetics ; Sus scrofa/immunology

Background: Natural preformed anti-pig IgM/IgG antibodies in primates play an important role in xenograft rejection. As it is not clear how IgE and IgA engage in the immune system in xenotransplantation, we investigated natural preformed and elicited anti-pig IgE/IgA in naive primates and after xenotransplantation in nonhuman primates.
Methods: The binding of IgM/IgG/IgE/IgA antibodies to red blood cells (RBCs) from wild-type (WT), α1,3-galactosyltransferase gene-knockout (GTKO), and GTKO/cytidine monophospho-N-acetylneuraminic acid hydroxylase gene-knockout/β-1,4 N-acetylgalactosaminyltransferase 2 gene-knockout (ie, triple-knockout pigs) pigs were measured by flow cytometry in naive human (n = 50) and baboon (n = 14) sera. Antibody binding to WT and GTKO pig RBCs (pRBCs) was also measured in the sera of baboons (nonsensitized n = 7, sensitized n = 2) and rhesus monkeys (nonsensitized n = 2, sensitized n = 11) following WT or GTKO pig organ/tissue xenotransplantation. Deposition of IgM/IgG/IgE/IgA in the grafts was detected by immunohistochemistry.
Results: The majority of humans had natural preformed IgM/IgG/IgE/IgA to WT and GTKO pRBCs. In contrast, IgM/IgG/IgE/IgA to triple-knockout pRBCs were present at lower levels and frequency (P < 0.01). Baboons also had IgM/IgG/IgE/IgA antibodies against WT pRBCs, but fewer to GTKO and triple-knockout (P < 0.01). After xenotransplantation into nonhuman primates, when IgM/IgG increased, IgE/IgA also increased, but to a lesser extent. In addition to IgM/IgG, IgE or IgA deposition was observed in rejected pig xenografts.
Conclusions: Primates develop serum anti-pig IgE/IgA antibodies both naturally and during xenograft rejection. The pathophysiological role, if any, of anti-pig IgE/IgA antibodies remains unknown.
Competing Interests: D.A. is an employee of Revivicor, Blacksburg, VA. The other authors declare no conflicts of interest.
(Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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0 (Antibodies, Heterophile)
0 (Immunoglobulin A)
37341-29-0 (Immunoglobulin E)
EC 1.- (Mixed Function Oxygenases)
EC 1.14.18.2 (CMPacetylneuraminate monooxygenase)
EC 2.4.1.- (Galactosyltransferases)
EC 2.4.1.- (N-Acetylgalactosaminyltransferases)
EC 2.4.1.- (alpha-1,3-galactosyltransferase 1, porcine)
EC 2.4.1.165 (beta-1,4-N-acetyl-galactosaminyl transferase 2)

Date Created: 20200816 Date Completed: 20210208 Latest Revision: 20210506

20240829

10.1097/TP.0000000000003408

32796494