"May 2002" Includes bibliographical references (leaves 229-251) Describes the investigation of the alteration of ABH antigen expression on the surface of red blood cells in patients with haematological malignancies.

"May 2002" / Includes bibliographical references (leaves 229-251) / xv, 251 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Describes the investigation of the alteration of ABH antigen expression on the surface of red blood cells in patients with haematological malignancies. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 2003

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Errata inserted on back end paper. / Bibliography: leaves 226-254. / xviii, 261 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Describes the development of techniques to genotype and simultaneously assess allele dosage at the ABO locus using PCR and allele-specific restriction enzyme digestion. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1996

The HLA complex is the most polymorphic genetic system known in man. The frequency of the HLA class II antigens have been well studied in Caucasoids but little data is available concerning HLA antigen frequencies in Negroes. In this thesis the class II antigens, excluding HLA-DP, were studied in South African (SA) Negroes (Xhosa), Cape Coloureds ( a group of mixed racial origin) and SA Caucasoids using serological, cellular ( HTC typing) and Southern blot techniques. The results obtained for the SA Negroes were compared with those previously found in Nigerians and American Negroes. Marked differences in HLA distribution occurred between these groups, which in part may be explained by Khoisan admixture in the SA Negroes. In addition, striking frequency differences were observed between the three SA populations. For example, in the Xhosa the HLA-DR1, DR4, DR7, DRw8, DQw2, DQw3, Dw1 and Dw3 specificities were found at a significantly lower frequency, whereas HLA-DR3, DRw6 and Dw' RSH' were found at a significantly higher frequency compared with the SA Caucasoids. The frequency in the Cape Coloureds was intermediate between those of the Xhosa and Caucasoids. In the SA Negroes and Cape Coloureds, several new specificities were detected such as HLA-DRw18, DR2 LUM(CT), DRwl2x6, DRw8x14, Dw' RSH', Dw' JOH' and Dw' BME'. The HLA-DR and DQ haplotypes in significant linkage disequilibrium were similar in the three groups. However, several haplotypes with unusual DR and DQ combinations such as HLA-DRw17,DQw7; DR9, DQw2 and DR4, DQw5 were present in the SA Negroes and Cape Coloured families. Al though some of these unusual haplotypes could be explained in terms of recombination between the common haplotypes, none could be typed using a panel of well defined homozygous typing cells, suggesting that the response observed in mixed lymphocyte culture arises from separate molecular determinants. The data on HLA class II antigen frequencies presented in this thesis is essential for future studies on HLA and disease associations and for establishing population relationships. Knowledge of new HLA class II antigens in the various population groups is also important in renal transplantation as matching for HLA-DR antigens is known to improve graft survival.

Indiana University-Purdue University Indianapolis (IUPUI) / Solid organ transplantation is limited by available donor allografts. Pig to human transplantation, xenotransplantation, could potentially solve this problem if physiologic and immunologic incompatibilities are overcome. Genetic modifications of pigs have proven valuable in the study of xenotransplantation by improving pig to human compatibility. More genetic targets must be identified for clinical success. First, this study examines platelet homeostasis incompatibilities leading to acute thrombocytopenia in liver xenotransplantation. Mechanisms for xenogeneic thrombocytopenia were evaluated using liver macrophages, Kupffer cells, leading to identification of CD18, beta-2 integrin, as a potential target for modification. When disruption of CD18 was accomplished, human platelet binding and clearance by pig Kupffer cells was inhibited. Further, human and pig platelet surface carbohydrates were examined demonstrating significant differences in carbohydrates known to be involved with platelet homeostasis. Carbohydrate recognition domains of receptors responsible for platelet clearance Macrophage antigen complex-1 (CD11b/CD18) and Asialoglycoprotein receptor 1 in pigs were found to be different from those in humans, further supporting the involvement of platelet surface carbohydrate differences in xenogeneic thrombocytopenia. Second, immunologic incompatibilities due to antibody recognition of antigens resulting in antibody-mediated rejection were studied. Identification of relevant targets was systematically approached through evaluation of a known xenoantigenic protein fibronectin from genetically modified pigs. N-Glycolylneuraminic acid, a sialic acid not found in humans, was expressed on pig fibronectin and was identified as an antigenic epitope recognized by human IgG. These studies have provided further insight into xenogeneic thrombocytopenia and antibody-mediated rejection, and have identified potential targets to improve pig to human transplant compatibility.