CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Loss of Endothelial Surface Expression of E-Selectin in a Patient With Recurrent Infections

Neutrophil accumulation at sites of inflammation is mediated by specific groups of cell adhesion molecules including the b2 (CD18) integrins on leukocytes and the selectins (Pand E-selectin on the endothelium and L-selectin on the leukocyte). This is supported by studies of patients with leukocyte adhesion deficiency syndromes whose leukocytes are genetically deficient in the expression of b2 integrins or selectin carbohydrate ligands (eg, sialyl-Lewisx). However, inherited deficiency or dysfunction of endothelial cell adhesion molecules involved in leukocyte recruitment has not been previously described. In this report we describe a child with recurrent infections and clinical evidence of impaired pus formation reminiscent of a leukocyte adhesion deficiency syndrome, but whose neutrophils were functionally normal and expressed normal levels of CD18, L-selectin, and sialyl-Lewisx. In contrast, immunohistochemical staining of inflamed tissue from the patient showed the absence of E-selectin from the endothelium, although E-selectin mRNA was present. However, E-selectin protein was expressed as significantly elevated levels of circulating soluble E-selectin were detected, the molecular size of which was consistent with a proteolytically cleaved form of E-selectin. Gene sequencing failed to show evidence of a secreted mutant variant. These data represent, to our knowledge, the first description of a potentially inherited dysfunction of an endothelial cell adhesion molecule involved in leukocyte recruitment and provide additional human evidence of the importance of endothelial selectins in the inflammatory response. r 1999 by The American Society of Hematology.