Identification of α-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man

Autor: F. A. Neethling, David K. C. Cooper, A.H. Good, N. Zuhdi, A.J. Malcolm, Eugen Koren, Rafael Oriol, Egidio Romano, Y. Ye, R.M. Ippolito
Rok vydání: 1993
Předmět:
Zdroj: Transplant Immunology. 1:198-205
ISSN: 0966-3274
DOI: 10.1016/0966-3274(93)90047-c
Popis: Human anti-pig antibodies were obtained by perfusing pig hearts (n = 4) and kidneys (n = 8) with human AB or O plasma followed by elution with 3 M NaSCN. The antibodies were screened against a panel of 132 synthetic carbohydrates conjugated to bovine serum albumin using an enzyme-linked immunoassay. An anti-immunoglobulin antibody was also used to detect immunoglobulin deposits on pig tissues. Four carbohydrate molecules with a terminal alpha-galactose residue bound all but one of the human anti-pig kidney antibodies and most of the anti-pig heart antibodies. These were: (i) alpha Gal(1--3)beta Gal(1--4)beta GlcNac (linear B type 2); (ii) alpha Gal(1--3)beta Gal(1--4)beta Glc (linear B type 6); (iii) alpha Gal(1--3)beta Gal(B disaccharide); and (iv) alpha Gal(alpha-D-galactose). Immunoglobulin deposition was documented post-plasma perfusion in all pig hearts and particularly strongly in all pig kidneys. These results suggest that human anti-pig antibodies are mainly directed against alpha-galactosyl structures. Extracorporeal immunoadsorption of human plasma through columns of the specific synthetic carbohydrate(s) might lead to depletion of anti-pig antibodies and allow discordant xenografting in man. Alternatively, the infusion of the specific carbohydrate(s) for a period of several days might result in neutralization of the anti-pig antibodies and allow accommodation to take place.
Databáze: OpenAIRE