Chronic urticaria: novel clinical and serological aspects

Background Recently, distinct studies have shown that: (a) chronic idiopath ic urticaria (CIU) is autoimmune in 30-50% of cases; (b) in patients with C IU the autologous serum skin test is inhibited by heparin; and (c) basophil histamine release induced in vitro by CIU sera maybe complement-dependent. Objective To carry out a comprehensive clinical and serological study on CI U based upon these observations. Methods Three hundred and six adults with CIU underwent intradermal (ID) te st with autologous serum; 57 of them with autologous heparinized plasma as well. Sera from 121 patients (plasmas from 17) were employed to induce in v itro histamine release from basophils of normal donors. The effects of heat ing (56 degreesC, 60 min), filtration through membrane, and preincubation w ith heparin were evaluated as well. Results Autologous serum and plasma induced a weal and flare reaction in 20 5 out of 306 (205/306; 67%) and in 8/57 (14%) patients, respectively. Posit ive plasma skin tests were observed only in patients showing strongly posit ive serum skin tests. Plasma did not elicit any skin reaction in 3/3 patien ts with dermatographism who showed a positive intradermal test with saline. Sera from 20/121 (16.5%) patients induced significant histamine release fr om basophils of normal donors. 19/20 sera were from patients with a positiv e intradermal test; thus, basophil histamine release assay was positive in 19/87 (21.8%) patients with a positive serum skin test. Heating at 56 degre esC x 1 h markedly reduced the histamine-releasing activity of both serum a nd plasma from in vitro reactors. Ultrafiltered fractions > 100 kDa of both sera tested retained the histamine-releasing activity, whereas fractions < 100 kDa were not able to induce any histamine release. Heparin dose-depend ently inhibited histamine release induced by sera and plasma, and by basoph il agonists such as anti-IgE, formyl-methionyl-leucyl-phenilalanine, and in terleukin (IL)-3. Conclusions 67% of our patients with CIU showed a positive autologous serum skin test. Sera from about 20% of those positive on autologous serum skin test induced histamine release from normal basophils in vitro probably as a consequence of the presence of functional autoantibodies. The marked diffe rence between in vivo and in vitro findings could reflect the existence of a mast cell-specific histamine-releasing factor which does not release hist amine from basophils of healthy blood donors. However, it might be also the result of in vivo priming of patients' cutaneous mast cells or of heteroge neity of basophil donors. At least in some cases complement seems essential for histamine-releasing activity of serum from patients with CIU. Heparin inhibits histamine release from both basophils (in vitro) and mast cells (i n vivo), probably acting directly at a cellular level.