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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