Similarities in the immunoglobulin response and VH gene usage in rhesus monkeys and humans exposed to porcine hepatocytes

作者: Joanne L Zahorsky-Reeves , Clare R Gregory , Donald V Cramer , Insiyyah Y Patanwala , Andrew E Kyles

DOI: 10.1186/1471-2172-7-3

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摘要: Background The use of porcine cells and organs as a source xenografts for human patients would vastly increase the donor pool; however, both humans Old World primates vigorously reject pig tissues due to xenoantibodies that react with polysaccharide galactose α (1,3) (αGal) present on surface many cells. We previously examined xenoantibody response in exposed hepatocytes via treatment(s) bioartficial liver devices (BALs), composed support matrix. determined BAL-treated are predominantly directed at αGal carbohydrate epitopes, encoded by small number germline heavy chain variable region (VH) immunoglobulin genes. The studies described this manuscript were designed identify whether responses IgVH genes encoding antibodies non-human used preclinical models similar those humans. Adult non-immunosuppressed rhesus monkeys (Macaca mulatta) injected intra-portally or heterotopically transplanted lobe. Peripheral blood leukocytes serum obtained prior multiple time points after exposure, immune was characterized, using ELISA evaluate levels specificities circulating xenoantibodies, production cDNA libraries determine B encode antibodies.

参考文章(48)
M.Z. Radic, L. Wang, U. Galili, Human anti-Gal heavy chain genes Journal of Immunology. ,vol. 155, ,(1995)
U Galili, F Anaraki, A Thall, C Hill-Black, M Radic, One percent of human circulating B lymphocytes are capable of producing the natural anti-Gal antibody Blood. ,vol. 82, pp. 2485- 2493 ,(1993) , 10.1182/BLOOD.V82.8.2485.2485
Marko Radic, Le Wang, Uri Galili, Human anti-gal heavy chain genes: Preferential use of VH3 and the presence of somatic mutations Journal of Immunology. ,vol. 155, pp. 1276- 1285 ,(1995)
T Eversole, K Meek, J D Capra, Conservation of the most JH proximal Ig VH gene segment (VHVI) throughout primate evolution. Journal of Immunology. ,vol. 146, pp. 2434- 2438 ,(1991)
CALVAS, APOIL, FORTENFANT, ROUBINET, ANDRIS, CAPRA, BLANCHER, Characterization of the three immunoglobulin G subclasses of macaques. Scandinavian Journal of Immunology. ,vol. 49, pp. 595- 610 ,(1999) , 10.1046/J.1365-3083.1999.00540.X
Erika F. Helmuth, Norman L. Letvin, D. H. Margolin, Germline repertoire of the immunoglobulin V(H)3 family in rhesus monkeys. Immunogenetics. ,vol. 51, pp. 519- 527 ,(2000) , 10.1007/S002510000170
Jing Pan, Sharda Naik, Henry Santangini, Donna Trenkler, Hugo Jauregui, Flow cytometric characterization of isolated porcine hepatocyte suspensions for liver support. Artificial Organs. ,vol. 20, pp. 1173- 1180 ,(2008) , 10.1111/J.1525-1594.1996.TB00658.X
L. Bühler, S. Deng, J. O'Neil, H. Kitamura, M. Koulmanda, A. Baldi, J. Rahier, I.P.J. Alwayn, J.Z. Appel, M. Awwad, D.H. Sachs, G. Weir, J.P. Squifflet, D.K.C. Cooper, Ph. Morel, Adult porcine islet transplantation in baboons treated with conventional immunosuppression or a non-myeloablative regimen and CD154 blockade. Xenotransplantation. ,vol. 9, pp. 3- 13 ,(2002) , 10.1034/J.1399-3089.2002.1O044.X
Hikaru Fujioka, Donald V. Cramer, Chikao Yasunaga, Phillip J. Tuso, Guo-Du Wu, Yvette Middleton, Albert D. Moscioni, Jacek Rozga, Achilles A. Demetriou, Leonard Makowka, Differential patterns of reaction of human natural antibodies to pig hepatocytes and vascular endothelium Liver Transplantation. ,vol. 1, pp. 85- 93 ,(1995) , 10.1002/LT.500010203