Chronic Urticaria Quality Of Life And Clinical Features Of The Investigation And Chronic Idiopathic Urticaria Basophils Related Research

Chronic urticaria is a common skin disease, manifested by recurrent erythema, wheal with itching (may be combined with angioedema), sustained at least six weeks. Its mortality rate is very low, therapy is usually effective, having very little damage to other organs or functions.Therefore, clinicians generally believed that it does not affect the life of patients. However, some scholars have recently reviewed some articles concerning the quality of life of CU patients, and showed that the impact on quality of life of CU patients was similar to a number of fatal diseases and other skin disease such as psoriasis, atopic dermatitis which were definitely affecting the life quality of patients.To assess the severity of a disease, we should not only concern their physical disease severity, but also the quality of life of patients. In this study, we first analyzed the life quality of chronic urticaria patients by WHOQOL-BREF scale.Studies showed there were some immune genetics, dietary habits and socio-economic status differences between the east and west, which resulting in some differences in clinical manifestation and laboratory aspects between different groups of CU patients. Currently, the domestic retrospective studies on the characteristics, course, prognosis of CU were limited and understanding was still insufficient. In order to get more information on clinical information, and then guide the laboratory in-depth study, therefore we analyzed 310 cases of CU patients retrospectively.Nowadays, nearly half of the CU patients having anti-IgE antibody and anti-FcεRI autoantibodies, should be classified as chronic autoimmune urticaria (CAU). Because the pathogenesis of the other CU patients is not fully understood, this type of CU was definited as chronic idiopathic urticaria (CIU). CIU is a common skin disease, the prevalence rate of about 1% in the United States, there are at least tens of millions of patients in China with a roughly estimatimation. The average disease duration was 3 to 5 years, and 20% of CIU patients was over 5 years. Research has shown that, CIU patients with impaired quality of life similar to patients with heart disease, and other skin diseases such as atopic dermatitis, psoriasis. In the United States, among CIU patients of teaching hospital (those who did not take immunosuppressive drugs), the average annual medical costs was more than 2000 U.S. dollars, so it is very necessary to further study its pathogenesis and to improve the treatment.Many studies support that mast cells and basophils play a role in the pathogenesis of CIU. Some people believed that basophils might be a circulating precursor mast cells, or mast cells are the "basophils within the organization." But the current evidence suggests that mature basophils are terminally differentiated granulocytes cycle, which can infiltrate into tissues and exudates during inflammatory or immune reaction, and it is a normal main source of histamine in the blood. On the contrary, the morphological matured mast cells are not circulating blood cells, they developed in blood and matured in tissues.In recent years, based on specific cell lines, monoclonal antibodies and high-purity cell sorting technology, it was found that basophils had important functions that people never know in allergic reactions and immune regulation.Previous studies found that CU patients'basophils have some characteristics different from the healthy population and patients with atopic diseases.In view of this, we chose basophils as our study cells.First, we used DNA microarray technologyto detect differentially expressed genes of the basophils of CIU patients. We built basophil cDNA library after screening CIU related differentially expressing genes. That would provide some useful clues for studying the pathogenesis of CIU. As the results showed that there was a total of 30 differentially expressed genes when compared the CIU patients with the healthy control group. Of which, there were 12 upregulated genes,8 downregulated genes,10 unknown function genes. Most of these differentially expressed genes were involved in intracellular signal transduction pathways, including the MAPK signal transduction pathways, Toll-like receptor signal transduction pathways and T cells and B cell signal transduction. In these signaling pathways, the lower expression of transcription activator protein 1 (AP-1) protein molecules (Jun and Fos) was particularly prominent.Gene expression is very complex, the same gene may play a different role in different conditions or at different times.Protein is the performer of all life function. Considering of the result that AP-1 protein expression was higher in some allergic diseases, we detected the c-jun, c-Fos, phospho-c-jun protein expressions by the WB method and the DNA binding activity of AP-1 family with TransAMTM AP-1 kit respectively. The results showed that phospho-c-jun (Ser73) protein expression was increased in CIU patients. There was also some changes in the field of DNA binding activity of AP-1 family factors, and these differences may be one of the pathogenesis of CIU. [Abstract] Objective:Evaluate the quality of life(QoL) of patients with chronic urticaria and explore its main influential factors. Methods:The clinical characters of two hundred and tenth patients with chronic urticaria were investigated and their quality of life were assessed. QoL was evaluated using the brief scale of quality of life of WHO(WHOQOL-BREF), which was consists of five subscales including 26 items. The statistical methods were used to make analyses, which including ANOVA, Spearman correlation and multiple linear regressions. Results:The scores of WHOQOL-BREF of chronic urticaria patients were relatively low. The main factors influencing QoL of CU were included family friction, appetite, self-assessment, visual analogy score(VAS) and dermatology symptom score. Conclusion:The quality of life of patients with chronic urticaria was relatively poor, Improving the family relationship and appetite of patients will contribute to the improvement of quality of life.ChapterⅡAnalysis of Clinical manifestation in 310 chronic urticaria[Abstract] Objective:To analyze the clinical profiles, possible causes or associated findings, treatment and prognosis of patients with chronic urticaria. Method:Data from 310 patients with chronic urticaria were analyzed retrospectively. Results: Chronic continuous urticaria was most common, accounting for 53.9% of all cases. The male:female sex ratio among all urticaria patients was about 1.08:1; Angioedema was reported as additional symptom in 40 patients. Fifty-eight patients had physical urticaria,18 patients (5.8%) had infectious causes. Antinuclear antibodies were positive in many patients, which occupied 18.0% of all patients. The positive percentage of Helicobacter pylori(HP) infection was 26.2%. Other possible causes were food, atopy, drugs, dyspepsia and collagen vascular diseases.36.1% of patients have wheal at night.6.8% of patients have family history of urticaria. Most of the patients responded well to Antihistamines. Conclusions:After detailed analysis of history and some laboratory tests,51% of patients found a possible cause, and contribute to the clinical treatment. Careful detailed history taking and physical examination are still very effective diagnostic tool to assist treatment.Chapter III Microarray analysis of altered gene expression of basophils in Chronic idiopathic urticaria[Abstract] Objective:To detect gene expression profiles of basophils in chronic idiopathic urticaria using microarray analysis. Method:Basophils were isolated from the peripheral blood from the two pairs of CIU patients and healthy controls, then total RNA were extracted; samples were first labeled with cRNA Markers, purified and dried, and then hybridyzed with chip. Data were analysed with LuxScan3.0 image analysis software. Finally, two times differences to the standard was identified significant difference. Results:There was a total of 30 differentially expressed genes. Of which, there were 12 regulated genes,8 downregulated genes,10 unknown function genes. Most of these differentially expressed genes were involved in intracellular signal transduction pathways including the MAPK signal transduction pathways, Toll-like receptor signal transduction pathways and, T cells and B cell signal transduction pathways. Conclusion:There existed some genes expression differences of basophils between CIU patients and normal controls, these differentially expressed genes may play a role in the pathogenesis of CIU.Chapter IV C-jun/c-Fos protein expression of basophils from the chronic idiopathic urticaria patients[Abstract] Objective:Detect the c-jun/c-Fos protein expression of basophils from Cchronic idiopathic urticaria patients. Methods:Separated the nuclear protein of basophils from CIU patients and healthy controls by basophils immunomagnetic separation technology and nuclear/plasma protein separation kit. then detected c-jun, c-Fos, p-c-jun protein expression by western boltting method. Results:There were no differential expression among c-jun, c-Fos, P-c-jun (Ser76) protein expression between CIU patients and the healthy controls. P-c-jun (Ser73) protein expression was higher in CIU patients than that in the healthy controls. Conclusions:The overexpression of P-c-jun (Ser73) protein of basophil in CIU patients may play a role in the pathogenesis of CIU.Chapter V Study on the DNA binding activity of AP-1 protein of basophils in chronic idiopathic urticaria[Abstract] Objective:To investigate the role of transcription activator protein 1 (AP-1) in the pathogenesis of chronic idiopathic urticaria (CIU). Methods:By using basophils immunomagnetic separation technology, nuclear/plasma protein separation method, TransAMTM AP-1 kit and so on,-we studied the DNA binding activity changes of the familial factor AP-1 in basophils of CIU patients. Results:DNA binding activity of Phospho-c-jun, c-fos, Fos-B, Jun-B, Jun-D factor were higher in CIU patients than those in the healthy controls, among which, the increase of Phospho-c-jun, c-fos was more significant. DNA binding activity of Fra-1 factor was lower in CIU patients than that in the healthy contros. Conclusions:Some changes in DNA binding activity of AP-1 of basophils of CIU patients may be important in the pathogenesis of CIU.