Cooper D K, Good A H, Koren E, Oriol R, Malcolm A J, Ippolito R M, Neethling F A, Ye Y, Romano E, Zuhdi N
Oklahoma Transplantation Institute, Baptist Medical Center, Oklahoma City 73112.
Transpl Immunol. 1993;1(3):198-205. doi: 10.1016/0966-3274(93)90047-c.
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.
通过用人AB型或O型血浆灌注猪心脏（n = 4）和肾脏（n = 8），随后用3M硫氰酸钠洗脱，获得人抗猪抗体。使用酶联免疫测定法，针对一组与牛血清白蛋白偶联的132种合成碳水化合物筛选这些抗体。还使用抗免疫球蛋白抗体检测猪组织上的免疫球蛋白沉积。四个带有末端α-半乳糖残基的碳水化合物分子与除一种人抗猪肾脏抗体外的所有抗体以及大多数抗猪心脏抗体结合。它们分别是：（i）αGal(1→3)βGal(1→4)βGlcNac（线性B型2）；（ii）αGal(1→3)βGal(1→4)βGlc（线性B型6）；（iii）αGal(1→3)βGal（B二糖）；以及（iv）αGal（α-D-半乳糖）。在所有猪心脏血浆灌注后均记录到免疫球蛋白沉积，在所有猪肾脏中尤为强烈。这些结果表明，人抗猪抗体主要针对α-半乳糖基结构。通过特定合成碳水化合物柱对人血浆进行体外免疫吸附可能会导致抗猪抗体耗竭，并允许在人体内进行异种移植。或者，输注特定碳水化合物数天可能会导致抗猪抗体中和，并促使适应性发生。
