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Charles Surh
면역 미생물 공생 연구단
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Human antibody reactivity against xenogeneic N-glycolylneuraminic acid and galactose-α-1,3-galactose antigen.

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Title
Human antibody reactivity against xenogeneic N-glycolylneuraminic acid and galactose-α-1,3-galactose antigen.
Author(s)
Hurh S; Kang B; Choi I; Cho B; Lee EM; Kim H; Kim YJ; Chung YS; Jeong JC; Hwang JI; Kim JY; Lee BC; Charles D. Surh; Yang J; Ahn C
Publication Date
2016-07
Journal
XENOTRANSPLANTATION, v.23, no.4, pp.279 - 292
Publisher
WILEY-BLACKWELL
Abstract
BACKGROUND: Despite the development of α1,3-galactosyl transferase-knockout (GTKO) pigs, acute humoral xenograft rejection caused by antibodies against non-Gal antigens, along with complement activation, are hurdles that need to be overcome. Among non-Gal antigens, N-glycolylneuraminic acid (Neu5Gc) is considered to play an important role in xenograft rejection in human. METHODS: We generated human embryonic kidney 293 (HEK293) cells that expressed xenogeneic Neu5Gc (HEK293-pCMAH) or α1,3Gal (HEK293-pGT) antigen and investigated the degree of human antibody binding and complement-dependent cytotoxicity (CDC) against these antigens using 100 individual human sera. RESULTS: Both IgM and IgG bound to α1,3Gal, while only IgG bound to Neu5Gc. Of the ABO blood groups, the degree of IgG binding to α1,3Gal was highest for blood group A. The degree of CDC against HEK293-pCMAH cells was significantly lower than that against HEK293-pGT cells. However, CDC against HEK293-pCMAH cells was significantly higher than that against control HEK293 cells. In addition, the severity of CDC against HEK293-pCMAH cells positively correlated with that against GTKO pig aortic endothelial cells (PAECs), suggesting that Neu5Gc is the main antigen in GTKO PAECs. Similar to antibody-binding activity, only IgG binding correlated with CDC against HEK293-pCMAH cells. The most common subclass of IgGs against Neu5Gc was IgG1, which typically induces strong complement activation. CONCLUSIONS: We showed that IgG-mediated CDC was detected in Neu5Gc-overexpressed HEK293 cells incubated with human sera; however, this antibody reactivity to Neu5Gc was highly variable among individuals. Our results suggest that additional modifications to the CMAH gene should be considered for widespread use of pig organs for human transplants. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
URI
https://pr.ibs.re.kr/handle/8788114/2770
ISSN
0908-665X
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Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
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