Electron Microscopy of Red Blood Cells Altered by Auto-Inimunity-Inducing Drugs

Abstract

The fact that levodopa, a drug used for the treatment of Parkinson''s disease induces a direct Coombs-positive reaction in about 15% of treated patients, indicating the presence of auto-antibodies against the patient''s red blood cells (RBCs), is well known. Another known fact is that only 1% of those patients do actually develop auto-immune haemolytic anaemia. In this paper, we describe our findings utilizing the direct ELISA, a method for measuring the presence of IgM and IgG auto-antibodies on the patients'' red blood cells (RBCs), as well as an indirect ELISA, testing the presence of antibodies in their serum. The tests were preformed on 8 patients, 7 of whom had been receiving the drug for long periods of time. Our results show that the serum antibodies precede the bound antibodies in a significant fashion and that the severity of the anaemia is directly related to the amount of auto-antibodies. Since auto-antibodies do not seem to be directed against the drug itself, some modification of the RBC must occur. For this reason, we attempted to determine whether patients receiving the drug show any morphological changes of their RBCs which could be determined by scanning electron microscopy (SEM) and whether these changes could be related to direct and indirect ELISA. In most levodopa-treated patients, a small number of echinocytes could be observed by SEM, while in 1 patient who suffered a severe anaemic phase, a very high percentage of the RBCs were echinocytes and spherocytes. In vitro treatment of normal human RBCs showed similar forms of transformed RBCs, possibly explaining the reason for the auto-immune response caused in patients with renal failure undergoing extracorporeal haemodialysis with formaldehyde-resterilizable membranes.