Evaluation And Its Mechanism Of Histamine-releasing Activity In The Sera Of Patients With Primary Acquired Cold Urticaria

Backgrand and Aims PACU is a specific type of urticaria which characterized by the rapid onset of pruritus, erythema, and swelling after a cold stimulus. The occurrence of PACU is necessarily associated with cold factors. Its clinical manifestation is deferred and pertinacious. It is poor response to general antihistamine, and relatively bad prognosis. Because of no clear allergen, pathogenesis of PACU is still unclear, and investigation of the mechanism and development of new effective therapies are very important. Recent research showed that several immunological features of PACU resemble those of CIU. PACU can be passively transferred to normal individuals, and cold-dependent histamine release can be obtained from skin biopsies, and suggest that PACU is due to IgE or IgM. Serum from patients with PACU may cause a wheal and-flare reaction on intradermal injection and may contain anti-IgE autoantibodies. In addition, some researchers found that histamine release from basophils and mast cells might not be mediated by the same factor. The purpose of this study is to evaluate the serum histamine-releasing activity of patients with PACU by using in vitro histamine release assays of mast cells and basophils, and to analyze active ingredient of sera from patients with PACU how to induce histamine release and its role in pathogenesis of PACU, and to explore function of endogenesis factors of patients with PACU, and offer laboratory data and background to exploitation of new methods in treatment of PACU. Materials and Methods Sera from 15 patients with PACU were filtred with microcon YM-100 membrane and decomplemented (Heating at 56℃×30min) respectively, and then were divided into Patient's whole serum group, >100kDfractions group, <100kDfractions group and Decomplemented serum group. These groups were employed to induce in vitro histamine release from human cutaneous mast cells and basophils from nomal donors respectively, and histamine was detected by a fluorometric method. Results We separated mast cells from foreskin of infants and basophils from nomal donors successfully, and then identified them with alcian blue 8GX, alcian blue pyridine variant and toluidine blue. Sera from patients with PACU released a significantly higher quantity of histamine compared with the control subjects (P<0.05). Ultrafiltered fractions( >100kD) of sera from patients with PACU retained the histamine-releasing activity, whereas the other fractions (<100kD) were unable to induce histamine release. Heating at 56℃×30min markedly reduced the histamine–releasing activity of sera from patients with PACU. And that histamine release from mast cells were inconsistent with from basophils. Conclusion We found that sera from some patients with PACU showed significantly histamine release activity. It is important in the pathogenesis of PACU by stimulating or facilitating degranulation of mast cells or basophils, and histamine releasing activity of serum was associated with the Ultrafiltered fractions ( >100kD). Furthermore in some cases complement seems essential for histamine-releasing activity of sera from patients with PACU. In addition, histamine release from mast cells and basophils might not be mediated by the same factor.