STUDIES OF A NEW GENETIC DISEASE CHARACTERIZED BY A DEFICIENT PMN LEUKOCYTE SURFACE GLYCOPROTEIN(S)

Abstract

Four unrelated pts (3 F, 1 M) with granulocytosis, delayed umbilical cord severance, periodontitis, &/or recurrent soft tissue infections were identified. Adhesion-dependent PMN functions (chemotaxis, adherence-spreading, aggregation, phagocytosis, orientation, & antibody-dependent cellular cytotoxicity) were significantly (p <.001 for each assay) diminished in each pt. All fathers, mothers or siblings (2 M, 1 F) were asymptomatic & demonstrated normal PMN functions. PMN homogenates of each patient demonstrated a severe deficiency (<5% normal) of a high M.W. glycoprotein (GP138) (SDS-PAGE). A NaB3H4 labelling technique indicated that GP138 represents a major surface GP complex of normal PMNs (11.4±7 μg/mg total protein), but was undetectable on the surface of pt PMNs. GP138 content of maternal or female sibling PMNs was diminished (mean = 3.3 μg/mg), but was normal (mean = 13.6 μg/mg) in paternal or male sibling suspensions. Monoclonal antibodies directed at the α & common β subunits of 3 leukocyte "adhesive" GPs (OKM1, LFA-1, P150,95) were employed to demonstrate the absence of each of these GPs on the surface of patient PMNs & diminished (10-50% normal) surface OKM1 & β on maternal or female siblings' PMNs (flow microfluorimetry). Thus, GP138 deficiency syndrome represents a new disorder(s) related to the absence of critical adhesive PMN GPs. Since males & females are affected & the carrier state can be detected only in females, its mode of genetic transmission is uncertain.