Chronic granulomatous disease. Studies of a family with impaired neutrophil chemotactic, metabolic and bactericidal function

A family is described in which a brother and sister, ages 24 and 20, respectively, had recurrent staphylococcal infections with predominantly cutaneous involvement. Studies of neutrophil phagocytic, metabolic and bactericidal activity provided strong evidence for the diagnosis of autosomally inherited chronic granulomatous disease. Neutrophils showed normal phagocytosis, but impaired killing of staphylococci and the absence of a phagocytic metabolic burst as measured by glucose oxidation, formate oxidation, superoxide generation, chemiluminescence, iodination, thyroxine degradation, estrogen binding and nitroblue tetrazolium reduction. Neutrophils from the mother showed normal values for these determinations. Unexpectedly, both patients also had marked impairment in the chemotactic responses of their neutrophils and in the level of chemotactic activity generated in their serum by activation of the complement system. These abnormalities in chemotaxis were associated with the presence in the patients' serums of an agent which inhibited the chemotactic response of normal neutrophils. This inhibitory material was stable on heating at 56 °C for 30 minutes and had a large molecular weight as evidenced by retention of inhibitory activity on dialysis and by elution characteristics on gel chromatography. Inhibition was predominantly cell-directed rather than chemotactic factor-directed. Although other patients with recurrent infections and defective chemotaxis related to serum inhibitors have been described, impaired leukocyte migration has not been generally recognized in patients with chronic granulomatous disease. It remains to be determined what the relationship between the leukocyte bactericidal and chemotactic defects is, what their relative contributions to increased susceptibility to infections are, and whether similar impairment of chemotaxis is present in other patients with chronic granulomatous disease.