Demonstration of antibody‐associated cellular cytotoxicity in patients with acute myelogenous leukemia before and after chemotherapy

Abstract

This study demonstrates that a cytotoxic serum reactivity not requiring the presence of complement appears in the sera of patients with acute myelogenous leukemia. The reaction is detected upon short-term incubation of sera in vitro with autochthonous mononuclear white blood cells from peripheral venous blood of patients at the acute stage of the disease. This reactivity was demonstrated in 18/18 patients. Generally, the cytotoxicity was low in patients at the acute stage of the disease, but increased after chemotherapy and reached the highest level at the onset of clinical remission or just before. No cytotoxicity could be demonstrated against autochthonous remission white blood cells. The serum activity could be absorbed and eluted from protein A-sepharose CL-4B and was recovered in the 7S-fraction of the sera after gel filtration on Sephadex G-200 and ion exchange chromatography. This indicates that the demonstrated cytotoxicity is due to immunoglobulins of IgG-class. It is believed that Fc-receptor-bearing cells present in the target cell preparations function as effector cells. The reaction is designated antibody-associated cellular cytotoxicity (AACC).

A 125I-protein A-binding assay detecting antibodies to cell surface antigens

“…The results were similar to those obtained with the cytotoxic techniques [8,9]. The results were similar to those obtained with the cytotoxic techniques [8,9].…”

“…The present investigation of humoral immune response to LAA in acute leukemia, like a few other studies of humoral immune reactivity against autochthonous leukemic cells [3,7,8,9,19], supports the existence of specific antibodies reactive with molecules linked to the leukemic cell surface. A number of recently published reports describe antigens claimed to be specific for leukemia detected by mouse [2], rabbit [5,20], simian [17], and human [1] antisera.…”

“…We have previously presented evidence for the appearance of cytotoxic antibodies reactive with autochthonous AML leukemic cells using 51Chromium-release techniques [8,9]. To allow the detection of specific noncytotoxic antibodies in AML and ALL in addition, a 125I-protein A-binding assay has now been established.…”

“…In previous studies we presented evidence for the presence of specific cytotoxic leukemia antibodies in adult patients with AML [8,9]. These antibodies could be detected only in undiluted sera or in sera at low dilutions, and most often only after successful chemotherapy.…”

Decreased Antibody-Dependent Cellular Cytotoxicity in Preleukemic Syndromes

“…A number of effector cells includ ing subpopulations of lymphocytes [Nel son et al, 1976;Sandilans et al, 1976;Evans et al, 1978], monocyte-macrophage cells [Mantovani et al, 1977] and neutro phils [Hafeman and Lucas, 1979] have been shown to mediate ADCC. Recently, several workers described the decreased ADCC potential of the peri pheral blood from patients with different types of leukemia [Faldt and Ankerst, 1979;, Fernandes et al, 1979;Platsoucas et al, 1980;Jakobisiak et al, 1981a], cancer [Stratton et al, 1977] and primary immu nodeficiency disorders [Karen et al, 1978].…”