P-177

Complement activation in the initial phase following pancreatic islet auto- and allo-transplantation

C. Pollard¹, W.Y. Chung¹, C. Drogemmuller², C. Stover³, C. Milner², M.A. Webb¹, S. Illouz¹, T. Radford², D. Al-Leswas¹, D.K. Bilku¹, P.T. Coates², G. Maddern⁴, A.R. Dennison^1
1 University Hospitals of Leiceter NHS Trust, Leicester, U.K.; ² Royal Adelaide Hospital, Adelaide, Australia; ³ University of Leicester, Leicester, U.K.; ⁴ The Queen Elizabeth Hospital, Adelaide, Australia

Objectives: Islet transplantation has the potential to offer a cure for Type I diabetes and may also prevent the onset of diabetes in patients who have undergone pancreatectomy for the treatment of chronic pancreatitis. The extent of the host response in the initial phase following islet transplantation is a determinant of transplant success. Complement has been found to be important in ischemia reperfusion injury but has not yet been studied in islet transplantation. Therapeutic blockade is theoretically possible and although agents, have been developed data is lacking that to date would support their use in allo- or auto-islet transplant patients.
Methods: Blood samples were collected during induction of anaesthesia, at the end of surgical reconstruction, end of operation, 1 hour, 3 hours, 5 hours and days 1-7 postoperatively. Classical (CP), alternative (AP) and mannose-binding lectin (MBL) complement pathway activities were assessed using the complement function screen kit (Euro-Diagnostica AB, Sweden). C3 and C4 were measured by nephalometry.
Results: C3 and C4 levels were decreased in the initial phase following islet infusion and gradually return to normal by day 7. There were no differences in total C3 and C4 levels between groups of patients receiving islet auto and allo transplantants. Complement activation or consumption was observed in all three pathways. However, the degrees of consumption varied between individual patients.
Conclusions: We have been able to show that complement activation is a sensitive measure during intra-portal islet infusion, with decreased levels which generally return to normal by day 7. If changes in complement activity levels prove to be important in determining the outcome following islet transplantation then any interference with complement activity with therapeutic intent will have to be instigated before day 7. Current work is addressing this possibility.

P-177

Complement activation in the initial phase following pancreatic islet auto- and allo-transplantation

C. Pollard¹, W.Y. Chung¹, C. Drogemmuller², C. Stover³, C. Milner², M.A. Webb¹, S. Illouz¹, T. Radford², D. Al-Leswas¹, D.K. Bilku¹, P.T. Coates², G. Maddern⁴, A.R. Dennison^1
1 University Hospitals of Leiceter NHS Trust, Leicester, U.K.; ² Royal Adelaide Hospital, Adelaide, Australia; ³ University of Leicester, Leicester, U.K.; ⁴ The Queen Elizabeth Hospital, Adelaide, Australia

Objectives: Islet transplantation has the potential to offer a cure for Type I diabetes and may also prevent the onset of diabetes in patients who have undergone pancreatectomy for the treatment of chronic pancreatitis. The extent of the host response in the initial phase following islet transplantation is a determinant of transplant success. Complement has been found to be important in ischemia reperfusion injury but has not yet been studied in islet transplantation. Therapeutic blockade is theoretically possible and although agents, have been developed data is lacking that to date would support their use in allo- or auto-islet transplant patients.
Methods: Blood samples were collected during induction of anaesthesia, at the end of surgical reconstruction, end of operation, 1 hour, 3 hours, 5 hours and days 1-7 postoperatively. Classical (CP), alternative (AP) and mannose-binding lectin (MBL) complement pathway activities were assessed using the complement function screen kit (Euro-Diagnostica AB, Sweden). C3 and C4 were measured by nephalometry.
Results: C3 and C4 levels were decreased in the initial phase following islet infusion and gradually return to normal by day 7. There were no differences in total C3 and C4 levels between groups of patients receiving islet auto and allo transplantants. Complement activation or consumption was observed in all three pathways. However, the degrees of consumption varied between individual patients.
Conclusions: We have been able to show that complement activation is a sensitive measure during intra-portal islet infusion, with decreased levels which generally return to normal by day 7. If changes in complement activity levels prove to be important in determining the outcome following islet transplantation then any interference with complement activity with therapeutic intent will have to be instigated before day 7. Current work is addressing this possibility.