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Individual Human Serum Differs in the Amount of Antibodies With Affinity for Pig Fetal Ventral Mesencephalic Cells and the Ability to Lyse These Cells by Complement Activation

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Abstract:

Xenografting pig fetal ventral mesencephalic (pfVM) cells to repair the dopamine deficit in patients with Parkinson’s disease is the focus of both experimental and clinical investigations. Although there have been marked advances in the experimental and even clinical application of these xenogeneic transplantations, questions regarding the host’s xenospecific immune response remain unanswered. It has been shown that human serum is able to lyse pfVM tissue by both anti-gal-gal and non-anti-gal-gal antibodies by complement activation. The aim of this study was to investigate whether interindividual differences exist in the levels of pfVM cell-specific IgM and IgG subclass antibodies, their ability to lyse pfVM cells in vitro and the relationship between both. Pig fetal VM cells were incubated with heat-inactivated serum from 10 different individuals and binding of IgM antibodies and IgG subclass antibodies to pfVM cells was analyzed by flow cytometry. The ability to lyse pfVM cells was analyzed exposing 51Cr-labeled pfVM cells to fresh serum or isolated IgM and IgG from the same individuals and subsequent determination of released 51Cr from lysed cells. Strong differences were found between individuals in the levels of pfVM cell-specific IgM antibodies: antibody levels differed up to 40-fold. pfVM-specific IgG1 and IgG2 levels were only detectable in a few individuals. The ability to lyse pfVM cells ranged from negligible lysis up to 66.5% specific lysis. There was a strong correlation between the levels of individual pfVM-specific IgM antibodies and the ability to lyse pfVM cells in vitro. Isolated IgM, but not IgG, was able to lyse pfVM cells in the presence of complement. In conclusion, the interindividual differences in the levels of IgM with affinity for pfVM cells and their ability to lyse pfVM cells in vitro are considerable. Only few individuals possessed IgG1 and IgG2 subclass antibodies with affinity for pfVM. These findings may influence patient selection for porcine transplants and chances of graft survival in individual patients.

Keywords: Complement-dependent cytotoxicity; Parkinson’s disease; Porcine; Ventral mesencephalon; Xenotransplantation

Document Type: Research Article

DOI: https://doi.org/10.3727/000000004783983503

Affiliations: 1: *Department of Neurosurgery, University Hospital Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands 2: †Medical Biology Section of Pathology and Laboratory Medicine, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands 3: ‡Department of Veterinary Anatomy and Physiology, University of Utrecht, Yalelaan 1, 3584 CL, The Netherlands 4: §Department of Cell Biology, Section Immunology, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands

Publication date: 2004-01-01

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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