IgE production is stimulated by IL-4 and inhibited by INF-γ. To examine the basis of the elevated serum IgE concentrations seen in patients with WAS, we analyzed in vitro IgE, IL-2, IL-4, IL-6 and IFN-γ production in 7 WAS patients and 19 pediatric controls. The mean age of our WAS patients was 58 months and the mean serum IgE concentration was 581 units/ml (range 30-1,634 units/ml).

Peripheral blood mononuclear cells (PBMC) were cultured in media alone, in the presence of 300U/ml of IL-4 and with IL-4 and anti-CD40 antibody. WAS patients and controls had similar spontaneous IgE production. Cells of controls produced more IgE in the presence of IL-4 alone than did cells from WAS patients (18,746 pg/ml vs 2830 pg/ml, p=0.037), but comparable levels were seen when cells were stimulated with IL-4 and anti-CD40 (control 102,725 pg/ml vs WAS 136,675 pg/ml, p = 0.33).

Cytokines produced by PBMC stimulated with PHA and PMA for 48 hours were measured using commercially available ELISA kits. The WAS patients had a mean IL-4 production of 2206 pg/ml compared to 1104 pg/ml in controls (p=0.026). Mean IFN-γ production in the WAS patients was 215.7 pg/ml compared to 1591.5 pg/ml in controls (p=0.0004). There was no significant difference in IL-2 and IL-6 production between the two groups.

These results indicate that the elevated serum IgE concentrations in patients with WAS may be due, at least in part, to abnormal regulation of cytokine production. These observations may be important for understanding the regulation of IgE synthesis in WAS patients as well as in the general population.