Mechanisms of Immune Lysis of the Red Cells in Hereditary

the binding of proportionately larger quantities of the third component of complement (C3) to these cells. The same amount of bound C3 was found on the membranes of normal and HEMPAS cells for a given degree of lysis. Hence, the marked increase in lysis of HEMPAS cells is due to the increased adsorption of antibody and/or increased binding of C4. PNH cells bound the same amount of C4 per bound C1 as normal cells but bound more C3 than normal cells. However, the mean concentration of C3 on the membrane of PNH cells was one-third to one-fifth that on normal cells for a given degree of lysis. Hence, the increased lysis of PNH cells is due to the increased binding of C3 and increased hemolytic effectiveness of the bound C3. Dr. Rosse is the recipient of Research Career Development Award no. 5 K04 Ca38862. Dr. Logue is a Research Associate at the Durham Veterans Administration Hospital. Received for publication 13 March 1973 and in revised form 24 August 1973. INTRODUCTION Normal red cells are not readily lysed by cold agglutinins and complement; lysis usually occurs only wheoi relatively large amounts of antibody and/or complement are used. The red cells in at least two blood disorders appear to be more readily lysed than normal red cells by anti-I cold agglutinins and complement. The red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH)1 have been extensively studied and have been shown to consist of at least two populations, one of which is markedly sensitive to the lytic action of complement (1, 2). This sensitivity is apparent when complement is activated either by antibody or by the alternate (properdin) pathway (3-6). The latter mechanism of activation is responsible for the lysis of PNH cells in acidified normal serum (3, 4). Crookston et al. reported that the red cells of patients with a form of congenital dyserythropoietic anemia characterized by multinucleated erythroblasts, are also lysed in acidified normal serum (7). They proposed the name hereditary erythroblastic multinuclearity with a positive acidified serum test, or HEMPAS; this 1Abbreviations used in this paper: ACD, acid-citratedextrose solution; Cl, C2, C3.. ., the first, second, third, etc. components of serum complement (a bar over the number indicates that the component is in its active form); CLS H5D, a unit of sensitivity to complement lysis, viz. the reciprocal of the dilution of complement 0.2 ml of which will lyse 50%yo of 2.2 X 10' sensitized red cells in a total volume of 1.5 ml; CoF, a factor derived from cobra venom which initiates the alternate pathway of C3 activation; EAC, red cells sensitized with antibody and coated with components of complement; HEMPAS, hereditary erythroblastic multinuclearity with a positive acidified serum test; PNH, paroxysmal nocturnal hemoglobinuria; VBS, veranol-buffered saline. The Journal of Clinical Investigation Volume 53 January 1974 -31-43 .31 Downloaded from http://www.jci.org on June 20, 2017. https://doi.org/10.1172/JCI107551