Inhibitory effect of heparin on skin reactivity to autologous serum in chronic idiopathic urticaria

Background: Most patients with chronic idiopathic urticaria (CIU) show cutaneous reactivity to intradermal injection of autologous serum. In some cases this reactivity is associated with the presence of autoantibodies directed against IgE or IgE receptors expressed on mast cells, whereas in others no autoimmune mechanisms can be documented. Objectives: The aims of this study were to compare the cutaneous reactivity to serum and plasma samples in a series of patients with active CIU and to address the mechanisms of the inhibitory effect exerted by heparin on the cutaneous responsiveness to the histamine-releasing factors (HRFs) present in CIU serum. Methods: Fourteen patients with CIU were injected intradermally with autologous serum, plasma (anticoagulated by either heparin or EDTA), or serum samples to which heparin had been added. The effects of heparin injection on cutaneous responsiveness to allergens was tested in 5 atopic patients. Moreover, in a set of experiments sera were also adsorbed with Sepharose-conjugated heparin. Results: All the patients had positive cutaneous reactions to autologous serum injection. When heparinized plasma was injected, negative reactions were observed in 12 of 14 patients, and a sizable reduction in the wheal- and-flare reactions was recorded in the remaining 2. Compared with results obtained with serum, no substantial change was observed in 6 of 8 patients injected with EDTA-anticoagulated plasma. When heparin was added to serum, abrogation of skin reactivity was seen; nonetheless, no change in the cutaneous response to allergens was associated with locally administered heparin in 5 atopic patients with no history of CIU. Finally, adsorption of CIU sera with solid-phase heparin abrogated the ability to induce cutaneous reactions in 5 of 7 patients, whereas in the remaining 2 a sizable reduction was observed. Conclusions: These data indicate that heparin is able to profoundly inhibit the cutaneous response to HRFs present in the sera of patients with CIU. Although the precise level of action of this heparin- mediated effect is unclear from present data, preliminary evidence seems to indicate that heparin could directly interfere with HRFs present in CIU sera.