The humoral immunosuppressive effects of blood transfusion in renal transplantation

Forwell, Margaret Anne (1986) The humoral immunosuppressive effects of blood transfusion in renal transplantation. MD thesis, University of Glasgow.

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Renal transplantation offers the optimal quality of life for the patient requiring renal replacement therapy. The main reason for renal allograft failure remains immunological rejection. The discovery that pretransplant blood transfusion is associated with decreased graft loss through rejection led to the introduction of elective transfusion protocols for renal dialysis patients. Despite extensive research, the mechanism of the blood transfusion effect on transplant outcome remains unclear. Of the many suggested explanations, one proposed by MacLeod and her colleagues, claimed that Fcg-receptor blocking antibodies were produced after blood transfusion and correlated with renal allograft survival. The initial aims of the work described in this volume were to confirm and extend these findings (MacLeod et al, 1982b). Using IgG prepared from whole serum by standard chromatography, the association between Fcg-receptor blocking activity and blood transfusion was confirmed for both uraemic and non-uraemic subjects. The development of Fcg-receptor blocking activity was shown over the course of elective transfusion of previously untransfused renal dialysis patients'. IgG. preparations from transfused subjects were shown to interact in vitro not only with B lymphocytes as previously described, but also with normal, allogeneic peripheral blood and T lymphocytes, thymocytes, polymorphs, platelets and spermatozoa. The pattern of reactivity did not correspond to the Fcg-receptor bearing cell populations. The significance in vivo of inhibition by IgG preparations from transfused subjects of polymorph phagocytosis and platelet aggregation remains uncertain. Perhaps relevant to attenuation of allograft rejection was inhibition of the mitogen response which was associated with IgG Fcg -receptor blocking activity. Confirmation of the presence of Fcg-receptor blocking antibodies in patients potentially immunosuppressed by blood transfused was followed by similar experiments using IgG preparations from patients exposed to a wide range of alloantigens, although not necessarily in blood. Patients with haemophilia were chosen, as a group who received clotting factor concentrates derived from multiple donors, and in whom there were recent reports of impaired indices of immune function. Like the recipients of blood transfusion, patients with haemophilia yielded IgG which blocked Fcg-receptors and inhibited the mitogen response of lymphocytes from normal subjects. Only a small proportion of the haemophiliac subjects were later found to have antibody against Human T cell Leukaemia Virus Type III, thought now to mark potential development of the Acquired Immunodeficiency Syndrome (AIDS). The epidemiology of AIDS, while consistent with unifactorial viral aetiology, led to suggestions that pre-existing immunosuppression may predispose to the expression of the virus. Reports of anti-lymphocyte antibodies in the serum of practising homosexual men, the risk group with the highest incidence of AIDS, stimulated experiments to assess the prevalence of Fcg-receptor blocking antibodies in AIDS patients and in homosexual men with no evidence of the syndrome. IgG preparations from both groups blocked Fcg-receptors . and inhibited the mitogen response of normal lymphocytes. Crossreactivity with spermatozoa may indicate that anti-lymphocyte antibodies are induced by rectal insemination. Although these experiments were performed before identification of the virus, and anti-viral antibody status was not checked, the preyalence of infection in comparable populations at the time of testing (1983) has been regarded as too low to account for these findings. Despite the demonstration of IgG Fcg-receptor blocking activity in subjects with acquired immune abnormalities, no association was found between renal allograft survival and pretransplant IgG receptor blocking activity, using a variety of donor and third party Fcg-receptor bearing cells. No conclusive explanation was found for the discrepancy between this and previous work (MacLeod et al, 1982a and b). Lest the method of preparation of IgG eliminate the suggested association with transplant outcome, pretransplant sera were instead separated into fractions of graded molecular weight. There was a highly significant correlation between renal allograft survival and Fcg-receptor blocking activity in the highest molecular weight fraction (>19S). Although the serum factor(s) responsible were not. identified, their presence appeared to be associated with previous transfusion of blood or blood products, and with diminished response to skin testing with Dinitrochlorobenzene. This may indicate that high molecular weight serum Fcg-receptor blocking factors are involved in non-specific depression of cell-mediated immunity following blood transfusion, and may be regarded as predictive of successful renal transplantation.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Medicine, Immunology
Date of Award: 1986
Depositing User: Enlighten Team
Unique ID: glathesis:1986-76591
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 14:05
Last Modified: 19 Nov 2019 14:05

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