Effects of sulphydryl inhibition on the erythrocyte in paroxysmal nocturnal haemoglobinuria.

Abstract

Summary. Normal erythrocytes exposed to high concentrations of sulphydryl‐containing compounds such as reduced glutathione, cysteine, and 2‐aminoethyliso‐thiouronium bromide (AET) acquire some in‐vitro properties of the PNH erythro‐cyte with increased sensitivity to acidified serum and cold‐antibody lysis. These findings suggested the possibility that an abnormality of membrane sulphydryl metabolism is a feature of PNH. Investigations were undertaken in five patients with PNH and a group of normals. Quantitative determination of measurable SH groups in haemoglobin‐free erythrocyte membranes failed to reveal a difference between PNH and normal. Normal erythrocytes exposed to AET had a marked reduction in measurable SH groups. The functional status of the membrane SH groups was studied by the in‐vitro effect of sulphydryl‐binding compounds, p‐chloromercuribenzoate (PMB) and p‐chloromercuribenzene sulphonate (PMBS).In all PNH cases an increased sensitivity to the haemolytic effects of SH blockade as compared to normal erythrocytes was noted. Studies with the inhibitor, PMBS, which acts only on the outermost surface of the membrane, revealed two types of erythrocytes in PNH, one highly vulnerable and the other behaving similarly to normal. Haemolysis occurred without inhibition of glycolytic activity as measured by lactate production or interference with the intracellular SH status. It appears that the PNH membrane defect is associated with an abnormality in the functional activity of membrane SH groups.