Immunotherapy and beta-cell replacement in type I diabetes mellitus

Linde, P. van de (2009)

Doctoral Thesis

Control of allo- and auto-immunity is important for pancreas and islet transplantations. In chapter 2 different mechanism of actions of humanized monoclonal antibodies against CD3 and CD25 versus ATG are described. ATG leads to depletion of auto-reactive T-cells by ADCC, CDC and apoptosis induction, while anti-CD3 and daclizumab inhibited T-cell autoreactivity in a non-depleting fashion. In chapter 3, our experience with induction therapy with ATG and daclizumab was reported. ATG Fresenius or daclizumab were well tolerated and equally effective in reducing the incidence of acute rejections in simultaneous pancreas kidney transplantation. Data in Chapter 4 imply that daclizumab is more specifically affecting diabetes related immune responses compared to ATG. Islet transplantation provides an attractive and less invasive alternative to whole-organ pancreas transplantation. In chapter 5 we demonstrated the ability of our T-cell monitoring methods to determine the fate of repeated islet allografts transplanted into patients that express repeated mismatches. In most pancreas transplantations the enteric drainage is favoured exocrine duct management. Facing a higher risk on anastomotic complications in enteric drained pancreas transplantations, primary bladder drainage may be the preferred option. In Chapter 6, we demonstrated that primary bladder drainage followed by enteric conversion is a safe and effective procedure.

• Diabetes Mellitus
• Pancreas transplantation
• Immunosuppression
• Monoclonal antibody
• Polyclonal antibody

• All authors: Linde, P. van de
• Supervisor: Terpstra, O.T.; Roep, B.O.; Fijter, J.W. de
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2009-12-16