Determining risk for extravascular haemolysis in paroxysmal nocturnal haemoglobinuria patients treated with eculizumab

Summary

Paroxysmal nocturnal haemoglobinuria (PNH) is a blood disorder characterised by the presence of cells in the blood stream that cannot protect themselves properly against the body's own immune system. The part of the immune system that damages the cells is called complement. Complement normally binds to infectious agents and forms a pore or a 'hole' in the membrane causing them to 'explode' and die by a process called lysis. Complement also binds to normal healthy human cells but they are protected by a special coating of complement-inhibitory proteins. In PNH patients, some of this coating is missing and the cells becomes susceptible to pore formation and lysis. The patients' red blood cells die, and they require blood transfusions.

Eculizumab is a drug that binds to the complement proteins, stopping them from killing patients' blood cells. However, for some reason, around 30% of patients still require blood transfusions.

We are investigating the differences in the complement proteins of patients that have this problem.  We are particularly interested in the function of complement proteins, C3 and complement receptor 1 (CR1). Small, common changes in these proteins in the general population change the way in which complement attacks cells in PNH patients; we believe that these changes also alter the way in which a patient responds to eculizumab. We wish to purify these complement proteins from the blood of healthy people and use them in laboratory assays to investigate the way in which these small changes affect the interplay between complement, eculizumab and poor response to treatment.

Organisation: This study is organised by Professor Claire Harris from Newcastle University. 

Participation: 2 volunteers took part in this study where they were asked to provide a 50ml blood sample.