ABSTRACT
Although the primary defect in HIES remains unidentified, several important immune-related functional abnormalities have been observed. Defective granulocyte chemotaxis is a common feature of HIES.15,16 In one report, three patients with HIES-like features demonstrated impaired neutrophil chemotactic responsiveness to ‘bacterial chemotactic factors’ isolated from E. coli culture, but preserved mobility, phagocytosis, and bactericidal activity.17 Witemeyer and Van Epps18
observed similar abnormal neutrophil chemotaxis in two subjects with HIES, but not among their family members. Because of the variability in the expression of this phenotype, defective neutrophil chemotaxis is not considered a reliable marker of the HIES. There is evidence that this defect may be due to the production of an inhibitor, as sera from affected individuals can inhibit neutrophil chemotaxis from normal controls.19 This may be due to circulating immunecomplexes,16,20 and anti-IgE IgG antibodies directed against the Fc portion of IgE have been observed in subjects with HIES.21 Abnormalities in T cell function, including selective deficiency of suppressor (CD8+) T cells and enhanced in vitro production of total serum IgE, have also been observed in patients with HIES.22 Others have noted impaired T cell response to cytokines, suggesting an underlying defect in T cell signaling.23-26
GENETICS
A significant genetic etiology of HIES is supported by a number of studies showing familial aggregation of this disease.12,15,16 Although most cases of HIES appear to be sporadic, detailed examination of relatives of affected individuals often reveals evidence of subclinical disease in these individuals, including elevated serum immunoglobulin E levels, dental abnormalities, or distinct facies.
