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A Study On The Association Of Cytotoxic T Lymphocyte Associated Antigen (CTLA-4) Gene Polymorphisms With Bronchial Asthma In Children

Posted on:2005-04-22Degree:MasterType:Thesis
Country:ChinaCandidate:L QianFull Text:PDF
GTID:2144360125950598Subject:Academy of Pediatrics
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Bronchial asthma is a chronic allergic inflammatory disorder of the airways whose predominant pathological feature is the infiltration with eosinophile[34], and is a common chronic respiratory system disorder in children. Its clinical symptoms are recurrent episodes of wheezing, expiratory dyspnea, chest tightness and cough, which usually occur at night and or in the morning, and could be released spontaneously or with appropriate treatment. People of any age could suffer from asthma. The morbidity in children is about 1.54%, while just about 1% in adult. Environmental pollution becoming more and more serious in the industrial age, the morbidity and mortality of asthma show ascending trend year by year, which have already influenced not only the quality of people's life but also the growth of children, and have aroused great attentions from many scholars. Involving lots of factors such as heredity, environment and immunity, the asthmatic etiopathology is so complicated that even now we can't fully understand it. It has not being found out that persistent inflammatory response was demonstrated in bronchial mucosal biopsy specimens, even from mild asthmatic children until the late of 1970. The important characteristic features of this disease are chronic allergic airway inflammation, reversible airflow limitation and airway hyperresponsiveness. It is now accepted that the airways' chronic allergic inflammation is the essence of asthma, and the lopsided proportion of Th1 cells to Th2 cells is its characteristical immune abnormality, with increasing numbers and sthenic function of Th2 subtype, and decrease of Th1 subtype. Th2 cytokines secreted by activated CD4+ T cells play a crucial role in the forming and lasting of the delayed asthmatic response (including activating of eosiphils, airway hyperresponsivness, airway obstruction). And the activating of T lymphocyte cells needs two necessary stimulatory signaling pathways: the first signal pathway (antigen-specific TCR signal pathway) and the second signal pathway (costimulatory signal pathway). Cytotoxic T lymphocyte associated antigen-4 (CTLA-4), a receptor living on the enabled T lymphocyte, is one of the important molecules involved in the second pathway. Heredity plays a contributing role in the asthmatic etiopathology. Many asthmatic children have atopic constitution such as obesity, a history of allergic rhinitis, a history of eczema, and usually the similar histories could be found out from their first or second grade kinsman. With the development of molecular biology and genetics, the relationship between genes and asthma has been known through many methods such as genotype screening, candidate gene selecting and linkage analysis. Especially, it has been identified that the region 5q31-33 harbors a number of asthmatic susceptibility genes. Today many researchers believe that asthma is a kind of polygenic inheritant disease, whose heritability is about 70%-80%, with apparent familial gathering trend. Therefore, the research of molecular genetics about asthma such as candidate gene screening has become a focus in the world research domain. Cytotoxic T lymphocyte associated antigen 4 (CTLA-4) belongs to the superfamily of immunoglobin, and is a kind of important negative regulating factors. Competed with CD28, CTLA-4 binds to B7 situating at antigen presenting cell (APC), blocks the T lymphocytes' activating and proliferating, regulates the balance of Th1/Th2, mediates the down-regulation of T cell response, and maintains the balance humoral immunity and cellular immunity. The factor lies on 2q33, including 3 extrons and 1 presequence. Four polymorphisms of CTLA-4 have been found out, including extron3 (AT)n poly sequence, extron1 (+49A/G), promoter (-318C/T), 159C/G,which have many important biological meanings. And it has been identified that they are involved in the pathophysiological process of many autoimmune diseases and allergic diseases such as thyroid disease and diabetes. Similarly, in the process of asthmatic alle...
Keywords/Search Tags:Bronchial asthma, Children, Cytotoxic T lymphocyte associated antigen-4 (CTLA-4), Gene polymorphism, Polymerase chain reaction(PCR)
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