Effects of complement inactivation and IgG depletion on skin reactivity to autologous serum in chronic idiopathic urticaria

Abstract

Background: Intradermal injection of autologous serum elicits a wheal-and-flare response in about 60% of patients with chronic idiopathic urticaria (CIU). This reactivity has been attributed to the presence of IgG autoantibodies directed against IgE or the α-chain of the high-affinity IgE receptor (FcεRIα) expressed on basophils and mast cells, leading to the hypothesis that at least some forms of CIU could be sustained by an autoimmune process. Objectives: The aim of this study was to investigate the relationship between the presence of anti-IgE or anti-FcεRI antibodies and the ability to induce wheal-and-flare responses in CIU sera selected for the capacity to give a positive skin test response. Methods: Fifteen patients with CIU and a positive skin test response to autologous serum were injected intradermally with native serum and with serum heated at 56°C for 30 minutes and then adsorbed on Sepharose-protein G to obtain IgG depletion. Serum levels of anti-IgE and anti-FcεRIα antibodies were measured by ELISA by using purified IgE and recombinant RIα-soluble double-fusion protein RIα-human serum albumin-RIα, respectively. The histamine-releasing activity of sera was tested by using ELISA with whole human blood from a healthy donor. Results: All patients had positive cutaneous responses to native serum injection. Anti-FcεRIα antibodies were present in 14 of 15 native sera, only two of which were able to induce in vitro basophil degranulation. On the contrary, detectable amounts of anti-IgE antibodies were not found in any serum. IgG depletion by protein G resulted in complete (10/14 samples) or considerable (4/14 samples) removal of anti-FcεRIα antibodies. The two sera endowed with functional activity lost their capacity to trigger histamine release from basophils after heating and protein G adsorption. Nonetheless, heat-decomplemented/IgG-depleted sera elicited wheal-and-flare reactions comparable with those observed with untreated sera. Conclusions: These results strongly suggest that skin reactivity to autologous serum could be due to as yet unidentified non-Ig reactants present in the sera of patients with CIU.