The membrane abnormality of the red cell in paroxysmal nocturnal haemoglobinuria.

Abstract

IN paroxysmal nocturnal haemoglobinuria (PNH) a membrane abnormality renders the red blood cell (RBC) extremely sensitive to the lytic action of complement1. The nature of the abnormality is unknown: an alteration of the cell lipids has been postulated on the basis of the results of some lipid determinations2–8 and the greater tendency of lipids to form peroxides after exposure to ultraviolet light or H2O29–11. Alteration of the membrane proteins has also been proposed as the cause of the cell abnormality12,13. It has been found that treatment with some sulphydryl compounds renders normal RBCs similar to those in PNH in many respects14. In particular, they display a sensitivity to complement lysis twenty-fold greater than normal15 and have a very low acetylcholinesterase activity16. Among the sulphydryl compounds so far examined14,17–20 the radio-protector AET (2-amino-ethyl-isothiouronium bromide) has been shown to be the most effective in producing the PNH-like abnormality21. The PNH-like alteration induced in normal cells by sulphydryl compounds has not yet been identified, although it seems to involve the breaking of membrane disulphide bonds21. We have studied PNH and AET RBC membranes in parallel using sodium dodecyl sulphate (SDS) electrophoresis in Polyacrylamide gels. Our experiments show further similarities between PNH and AET cells and indicate that, in both, the alteration (or at least part of it) is located in the protein moiety of the membrane, where an abnormal polypeptide chain is demonstrable.