DEFECTIVE ADHERENCE-MEDIATED POLYMORPHONUCLEAR LEUKOCYTE (PMN) ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY (ADCC) IN PATIENTS WITH PMN SURFACE GLYCOPROTEIN 138 (GP 138) DEFICIENCY

Abstract

Four unrelated patients with GP 138 deficiency, marked leukocyte adherence defects, and normal IgG Fc receptors (PMN-EA rosettes = 84±6%) were studied for the ability to mediate PMN and Mononuclear cell (MC) ADCC and MC natural killer cytotoxicity (NKC) in a 51Cr assay to herpes simplex virus-infected Chang liver cells. At multiple effector to target cell ratios (E:T), patients' PMN-ADCC was absent (E:T 100:1, 4.3±1.2) and significantly lower than that of adults (27.9±8.1, p<.025), infants (15.3±4.2, p<.005) or cord blood (34.7±6.5, p<.001). Patients' MC-NKC (E:T 30:1, 10.0±4.3, controls 39.6±9.4, p<.05) and MC-ADCC (E:T 30:1, 27.6±11.4, controls 45.2±7.6) were markedly lower than controls but variable. A single cell agarose conjugation assay demonstrated that anti-HSV IgG increased the percentage of normal PMN conjugation (from 1.5±0.5 to 4.5±0.8, p<.01) but had no effect on conjugation of patients' PMN (1.2±0.2 to 1.0±0.2). Low MC cytotoxicity was due to lytic defects. This model demonstrates for the first time that PMN-ADCC is dependent on an adherence-mediating leukocyte surface glycoprotein GP138 to mediate target binding in addition to intact IgG Fc receptors.

Supported by NIH grant HD 13021

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