Regulation of IgE and IgG4 synthesis in patients with hyper IgE syndrome

In order to investigate the imbalance of IgG subclasses and its relationship to IgE level, 14 patients with hyper IgE syndrome (HIE syndrome) were examined for serum IgG subclasses and IgE levels and five of these patients were studied for in vitro IgE and IgG subclass production by peripheral blood lymphocytes (PBL) in response to interleukin-4 (IL-4)/interferon-gamma (IFN-gamma). Serum IgE levels were highly correlative with serum IgG4 levels (r = 0.75, P less than 0.005), but not with IgG1, IgG2 or IgG3 levels (r = 0.21, 0.43 and 0.41, respectively). In an in vitro study, recombinant IL-4 enhanced not only spontaneous IgE synthesis but also IgG4 synthesis in cultures of PBL from patients with HIE syndrome as well as in healthy donors (P less than 0.01), and the effect of recombinant IL-4 on both IgE and IgG4 synthesis was inhibited by low concentrations of recombinant IFN-gamma (P less than 0.01). The disturbed regulation of IgE and IgG4 seen in patients with hyper IgE syndrome may be caused mainly by the disturbed regulation of both cytokines.