Intrinsic polymorphonuclear chemotactic defect in a boy with chronic granulomatous disease

A six year old boy is described who suffured from recurrent and protracted infections of multiple organs by various catalase positive bacteria. A severe episode of osteomyelitis involving several bones was caused by Aspergillus fumigatus. Studies of his PMNs revealed impaired metabolic as well as microbicidal functions characteristic of CGD. Chemiluminescence in response to both opsonized zymosan and sodium fluoride was markedly depressed, while control PMNs showed significant responses. Control leukocytes suspended in patient's serum likewise evoked normal chemiluminescence. Microbicidal activity against staphylococcus aureus 502A was also decreased using patient's PMNs, whereas control PMNs were able to reduce the number of colony forming bacteria by 2 logs in 120 minutes. Viable intracellular bacteria after lysis of extracellular bacteria formed 3 X 10(7) colonies from patient's PMNs and less than 2 X 10(5) colonies from the control. NBT dye reduction studies of the family members suggested an x-linked recessive mode of inheritance. The extraordinary nature of this case lies in the discovery of an associated intrinsic cellular defect of chemotaxis involving his polymorphonuclear leukocytes. Specifically, the Rebuck skin window showed predominantly mononuclear cells from 4 up to 24 hours. In addition, the patient's PMNs failed to migrate in response to cultured filtrates of E. coli as the chemoattractant. This abnormality persisted in the presence of autologous plasma or serum as well as in control plasma or serum. Control PMNs showed normal chemotaxis in the presence of the patient's plasma or serum. The extent to which the rare coexistence of these two phenomena influence the clinical disease is not known and remains to be elucidated.