Researches On CC Chemokines In The Pathogenesis Of Chronic Urticaria And The Clinical And Laboratory Study On Specific Immunotherapy For The Treatment Of Chronic Urticaria

Chronic urticaria is characterized by recurrent wheals and pruritus for at last 6 weeks and mainly caused by IgE mediated type I allergy. The cross-linking of IgE and its receptor can induce degranulation of mast cell and mediator release. The most important component is histamine. Recent researches raise the definition of late-phase allergic reactions. In addition to the function of histamine, chemokines, eosinophil, T lymphocyte and its cytokines also play an important role in the pathogenesis of chronic urticaria. The functions of cells and mediators related to the late-phase allergic reactions in the pathogenesis of chronic urticaria are hot researches now. But the relationship between chemokines and chronic urticaria is still unclear. Now, H1 receptor antagonist is mainly used for the treatment of chronic urticaria. In addition to the anti-histamine drugs, more and more specific immunotherapy is used for the treatment of chronic urticaria. But currently, there are mostly clinical observations to judge the treatment efficacy of specific immunotherapy and lack of comparative studies. It is also unclear whether the influence of specific immunotherapy on chemokines has relation with its treatment efficacy for chronic urticaria.The aim of this study is to investigate the mRNA expression of RANTES, MCP-1,3, MIP-1α in the patients with chronic urticaria and the correlations between these CC chemokines and other mediators, so as to clarify the function of CC chemokines in the pathogenesis of chronic urticaria and offer the evidence for the treatment. At the same time, the study is to primarily explore the treatment efficacy of specific immunotherapy and its influence on the level of RANTES and MCP-1, so as to provide the clinical and laboratory evidence for specific immunotherapy.The reverse transcription-polymerase reaction (RT-PCR) technique was applied to semiquantitatively analyze the mRNA expression of RANTES MCP-1 MCP-3 and MIP-1 α in the peripheral blood mononuclear cells (PBMCs) from 31 patients with chronic urticaria and 22 healthy subjects in the first part, at the same time, the mRNAexpression of these CC chemokines in the lesions from 12 patients and 11 healthy subjects were also detected. The correlations between the mRNA expression of these CC chemokines in PBMCs and the level of IgE and ECP were also investigated. In the second part, the allergens were detected in patients with chronic urticaria, chronic eczema and healthy subjects by skin prick test. The positive rates were compared among these three groups, especially the positive rates of DF (Dermatophagoides farinae). Subsequently, ELISA (quantitative sandwich enzyme-linked immunosorbent assay) was applied to analyze the serum level of RANTES MCP-1 in the active and inactive chronic urticaria patients with allergy to DF, compared with healthy controls, so as to determine the relationship and significance between CC chemokines and activity of chronic urticaria. In the third part, the chronic urticaria patients with allergy to DF were randomly divided into two groups: Group A received specific immunotherapy and mizolastine (10mg/d) in the active phase; Group B only received mizolastine (10mg/d) in the active phase. The difference of treatment efficacy, the level of RANTES and MCP-1 between these two groups were studied.The results of the first part showed that the mRNA expression of RANTES . MCP-1 MCP-3 and MIP-1 α in PBMCs were significantly higher in chronic urticaria patients than normal controls and the level of RANTES. MCP-1 in lesions were also higher in chronic urticaria patients (P<0.001). But there is no significant difference on the mRNA expression of MCP-3 and MIP-1 α in lesions between chronic urticaria patients and normal controls (P>0.05 ) . There is a positive correlation between the mRNA expression of RANTES and MCP-1 MCP-3, MIP-1 α in PBMCs from patients with chronic urticaria, and the mRNA expression of MCP-1 and MIP-1 α was also shown to have a positive correlation (P<0.05 ) . The mRNA expression of RANTES in lesions from chronic urticaria patients was also shown to have a negative correlation with MCP-1 (P<0.001) . But there is no correlation between MCP-1 and MCP-3. MCP-3 and MIP-1 α , and also no correlation between these CC chemokines in PBMCs and in lesions (P>0.05) . The mRNA expression of RANTES in PBMCs from patients with chronic urticaria was shown to have a negative correlation with serum level of IgE and ECP (P<0.05) . Subsequently, the results of the second part showed that the total allergen positive rate of chronic urticaria patients was 91.7%, higher than those of chronic eczema patients(75.0%) and normal controls(6.0%) (P <0.001) . Among the patients with chronic urticaria, 58.3% patients had skin sensitivity to DF , higher than those of chronic eczema patients(36.8%) and normalcontrols(6.0%) (P <0.01 and 0.001). The serum level of RANTES and MCP-1 were higher in active chronic urticaria patients allergy to DF than inactive patients and normal controls, and the level of RANTES and MCP-1 were also higher in inactive patients than normal controls (P <0.001) . At the same time, the level of RANTES in active patients with chronic urticaria was shown to have a positive correlation with MCP-1 (P<0.01) . The results of the third part showed that the total effective rate and SSRI( symptom score reduce index) of the group treated with specific immunotherapy were significantly higher than the control group in the 16th and 24th week after the treatment (P<0.05 and 0.0001) . The weekly urticaria episodes and anti-histamin drug dosages in specific immunotherapy group were decreased significantly (P<0.05 and 0.01). There was no significant difference on the incidences of adverse event between two groups (P>0.05) . On the other hand, the serum level of RANTES and MCP-1 were decreased significantly in the group treated with specific immunotherapy than control group in the 16th week after the treatment ( P<0.0001 and 0.01), in parallel with the clinical treatment efficacy.Thus, there are abnormal mRNA expression of RANTES, MCP-1,3 and MIP-1 α in chronic urticaria patients. DF is obviously a causative factor for chronic urticaria. The abnormal protein level of RANTES and MCP-1 play an important role in the pathogenesis of chronic urticaria allergy to DF, and are closely related to the activity of chronic urticaria. Specific immunotherapy shows the efficacy for the treatment of chronic urticaria, both in clinical and laboratory researches. It is worth to be recommended for the treatment of chronic urticaria patients with allergy to DP, especially for the severe perennial chronic urticaria patients, and can be used to be combined with H1 receptor antagonist.