Endogenous Immunosuppression and the Effect of Blood Transfusion on Cell Mediated Immunity in Haemodialysis Patients

Tsakiris, Dimitrios Ioannou (1990) Endogenous Immunosuppression and the Effect of Blood Transfusion on Cell Mediated Immunity in Haemodialysis Patients. PhD thesis, University of Glasgow.

Abstract

In order to clarify the effect of blood transfusion in uraemic patients, 48 dialysis patients who had not received previous blood transfusion were randomly allocated to receive 5 or 10 units of third-party packed cells at two week intervals. Twelve dialysis patients and 12 healthy subjects who had not received previous blood transfusion were also studied as control groups. The cell-mediated immunity (CMI) of the transfused patients was measured by skin testing with DNCB and four recall antigens before the first transfusion and 14 days after the last unit of blood. In addition, prior to the first and 14 days after each transfusion patients were screened for a) haematological and biochemistry results, b) cytotoxic antibodies, c) complement levels, d) titres of IgG secreting cells (PFC) in the peripheral blood both spontaneously and after stimulation with PWM and SAC, using a protein A plaque assay, and e) prostaglandin E (PGE) production in supernatants from both Con A-stimulated PBMC cultures and unstimulated ones. The two control groups were screened for these parameters on 3-4 occasions over a period of 3 months. The methods and results from this randomised controlled study are described in detail in the first 8 chapters of this thesis. In Chapter 9, I describe results from a large number of patients with regard to factors determining the response to DNCB and its value as a means of predicting renal allograft survival. This retrospective analysis was done from an angle and evidence provided by the prospective study. The aim of the study was, a) to assess the effect of blood transfusion in uraemic patients, b) to see whether patients with strong or weak reaction to DNCB differ in their response to transfusion, and try to define the optimum number of transfusions for each group to achieve a beneficial effect, c) to see whether blood transfusion-induced alterations in immune responses could be monitored with simple skin tests and d) to define possible factors determining the response to DNCB and assess the predictive value of the skin test regarding graft survival. In the group of the previously non-transfused dialysis patients more than half were strong DNCB responders. This proportion was two fold higher compared to that of the overall dialysis population. There was a progressive decline in strong responders as patients received more blood, and in multi-transfused patients CMI was profoundly suppressed. Multivariate analysis revealed that the most significant factor associated with the response to DNCB was blood transfusion. A number of factors did not show any association, namely age, sex, primary renal disease, type of dialysis, parity, ABO and rhesus blood groups, interval between last transfusion and test, cytotoxic antibodies and a number of haematological and biochemical parameters. HLA-DRW6 positive patients were more likely to be strong responders when tested prior to any blood transfusion, but the DRW6 effect was not observed in patients sensitised after one or more transfusions. This suggests that HLA-DRW6 is a marker of strong CMI, but this strong response can be modified by transfusion. Sequential skin testing with DNCB and recall antigens did not reflect changes induced by transfusion, as repeated immunisation resulted in stronger anamnestic responses, regardless of the amount of blood or whether they were transfused at all. Follow-up DNCB skin testing showed that blood transfusion at the time of sensitisation to DNCB was a crucial event for secondary responses to DNCB. Patients eliciting a strong primary response retained and gave even stronger responses on subsequent tests regardless of transfusion status at the time of sensitisation to DNCB. Contrary to that, weak responders who were sensitised after transfusion showed a further depression in their secondary responses, while weak responders sensitised prior to any transfusion were more likely to show increased secondary responses. As a result of this, approximately one third of the latter patients changed to strong responders in follow-up tests. (Abstract shortened by ProQuest.).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Medicine, Immunology
• Date of Award: 1990
• Depositing User: Enlighten Team
• Unique ID: glathesis:1990-78234
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 Jan 2020 15:36
• Last Modified: 30 Jan 2020 15:36
• URI: https://theses.gla.ac.uk/id/eprint/78234