Fibronectin from alpha 1,3-galactosyltransferase knockout pigs is a xenoantigen

被引：12

作者：

Chihara, Ray K. ^{[1
]}

Lutz, Andrew J. ^{[1
]}

Paris, Leela L. ^{[1
]}

Wang, Zheng-Yu ^{[1
]}

Sidner, Richard A. ^{[1
]}

Heyrman, Alex T. ^{[1
]}

Downey, Susan M. ^{[1
]}

Burlak, Christopher ^{[1
]}

Tector, A. Joseph ^{[1
,2
]}

机构：

[1] Indiana Univ Sch Med, Indianapolis, IN 46202 USA

[2] Indiana Univ, Dept Surg, Hlth Transplant Inst, Indianapolis, IN 46204 USA

来源：

JOURNAL OF SURGICAL RESEARCH | 2013年 / 184卷 / 02期

关键词：

Xenotransplantation; Xenoantigen; Fibronectin; Antibody-mediated rejection; N-glycolylneuraminic acid; Neu5Gc; NON-GAL ANTIBODIES; N-GLYCOLYLNEURAMINIC ACID; CARDIAC XENOGRAFTS; MEGALIN GP330; REJECTION; CELLS; IDENTIFICATION; DEFICIENCY; ANTIGENS; KIDNEYS;

D O I：

10.1016/j.jss.2013.04.012

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

Background: Antibody-mediated rejection continues to be an obstacle for xenotransplantation despite development of alpha 1,3-galactosyltransferase knockout (GTKO) pigs. Fibronectin (Fn) from GTKO pigs was identified as a xenoantigen in baboons. N-glycolylneuraminic acid (Neu5Gc), similar to galactose alpha 1,3-galactose, is an antigenic carbohydrate found in pigs. We evaluated human antibody reactivity and performed initial antigenic epitope characterization of Fn from GTKO pigs. Materials and methods: GTKO pig aortic endothelial cells (AEC) were isolated and assessed for antibody-mediated complement-dependent cytotoxicity (CDC). Human and GTKO pig Fn were purified and analyzed using immunoblots. GTKO pig and human AEC absorbed human sera were assessed for CDC and anti-GTKO pig Fn antibodies. GTKO pig proteins were assessed for Neu5Gc. Immunoaffinity-purified human IgG anti-GTKO pig (hIgG-GTKOp) Fn using a GTKO pig Fn column were evaluated for cross-reactivity with other proteins. Results: GTKO pig AEC had greater human antibody binding, complement deposition and CDC compared with allogeneic human AEC. Human sera absorbed with GTKO pig AEC resulted in diminished anti-GTKO pig Fn antibody. Neu5Gc was identified on GTKO pig Fn and other proteins. The hIgG-GTKOp Fn cross-reacted with multiple GTKO pig proteins and was enriched with anti-Neu5Gc antibody. Conclusions: Removal of antigenic epitopes from GTKO pig AEC would improve xenograft compatibility. GTKO pig Fn has antigenic epitopes, one identified as Neu5Gc, which may be responsible for pathology and cross-reactivity of hIgG-GTKOp Fn. Genetic knockout of Neu5Gc appears necessary to address significance and identification of non-Neu5Gc GTKO pig Fn antigenic epitopes. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：1123 / 1133

页数：11

共 31 条

[1] Deficiency of N-glycolylneuraminic acid and Galα1-3Galβ1-4GlcNAc epitopes in xenogeneic cells attenuates cytotoxicity of human natural antibodies [J].