Immune lysis of normal human and paroxysmal nocturnal hemoglobinuria (PNH) red blood cells. I. The sensitivity of PNH red cells to lysis by complement and specific antibody.

Abstract

The cells of patients with paroxysmal nocturnal hemoglobinuria are markedly sensitive to lysis by complement and antibody. In the blood of each of 10 patients, 2 populations of red cells were found, one of which (the "sensitive" population) required about l/25th as much complement as normal cells for lysis of an equal proportion of the cells. The difference in sensitivity of the sensitive population occurs in a variety of antibodies and with both human and guinea pig complement. The other population (the "insensitive" population) required a mean of one-half as much C as normal cells for lysis. When PNH cells are fractionated according to density, sensitive cells are present in all fractions and in the highest proportion in the least dense (youngest) cells. There is a rough correlation between the proportion and sensitivity of the sensitive population of cells and the severity of the hemolytic process. The acidified serum lysis (Ham''s) test was found to lyse largely the sensitive population of cells. However, some cells in this population were not lysed, and some cells in the insensitive population were lysed by acidified serum. In 2 patients, a sensitive population of cells was present that was not detected by the acidified serum lysis test. A simplified version of the complement lysis sensitivity test is described that is more accurate than Ham''s test in the detection and quantitation of the proportion of cells in the sensitive population. The sensitivity of the cells in PNH to complement lysis is fundamental to the pathogenesis of the disease. As red cells, both normal and PNH, circulate, small amounts of complement are fixed to them by factors present in normal serum. Because of the marked sensitivity of the sensitive population of PNH cells to complement lysis, they are destroyed intravascularly by complement, whereas normal cells, being much less sensitive, are not.