DEMONSTRATION OF INDUCTION OF ERYTHROCYTE INOSINE MONOPHOSPHATE DEHYDROGENASE-ACTIVITY IN RIBAVIRIN-TREATED PATIENTS USING A HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY LINKED METHOD

The activity of inosine monophosphate dehydrogenase (IMPDH: EC 1.2.1.1 4) was measured in erythrocyte lysates using a non-radiolabelled metho d linked to reversed-phase liquid chromatography (RPLC). The mean acti vity in erythrocytes from healthy controls using this sensitive method was extremely low (mean 85 pmol/h per mg protein, range 4-183). The e levated erythrocyte IMPDH activity reported previously in hypoxanthine -guanine phosphoribosyltransferase (HPRT) deficiency was confirmed (me an 234 pmol/h per mg protein). Erythrocyte IMPDH activity of patients with other disorders of purine metabolism, or with leukaemias and lymp homas, showed no marked difference from controls, except in one instan ce - an immunodeficient child with purine nucleoside phosphorylase (PN P) deficiency, treated with Ribavirin, where a 30-fold increase in act ivity was found (2670 pmol/h per mg protein). Investigation of erythro cyte IMPDH in other immunodeficient children with normal PNP activity demonstrated that this grossly elevated erythrocyte activity was attri butable to induction of IMPDH by Ribavirin therapy.