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The Relationship Between HLA-DRB1 Polymorphism And Idiopathic Thrombocytopenic Purpura In Children

Posted on:2012-06-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:X H LiFull Text:PDF
GTID:1484303356473974Subject:Academy of Pediatrics
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Background:Idiopathic thrombocytopenic purpura(ITP), also known as autoimmune thrombocytopenic purpura, is the most common bleeding disorder in childhood. Recently,ITP is also called as immune thrombocytopenica because it is always associated with immune pathogenesis.It is divided into acute 1TP (aITP) and chronic ITP (cITP) in clinic based on the course of which exceeding six months. Up to date, the cause and the pathogenesis are completely unclear. Nevertheless, acute ITP and chronic ITP share some common features. For examples, they are both related to humoral immunity and (or) cellular immunity, and both show certain degrees of genetic predisposition. Human leukocyte alleles(HLA) are the major histocompatibility antigen system which can lead to strong rejection and the most complex and polymorphic genes in the human genome. They play many important roles in transplantation rejection and immunity. In recent years, many studies have reported the relationship between HLA-DRB1gene polymorphism and adult ITP, however few studies have reported the relationship between HLA-DRB1gene polymorphism and ITP in children.The Gram-negative bacterium Helicobacter pylori is widely known as a causative agent of gastritis and peptic ulcers and as a high-risk factor for the development of gastric cancer and mucosa-associated lymphoid tissue lympoma. There are increasing data on the H. pylori infection in idiopathic thrombocytopenic purpura and platelet count response after bacterial eradication. Genetic host factors have been suggested as cause of H. pylori associated ITP in adult. Veneri et al found that HLA-DRB1*11, *14 and HLA-DQB1*03 frequencies significantly higher and HLA-DRB1*03 frequency significantly lower in H. pylori-negative patients. Few studies have reported the relationship between susceptible Hp?HLA-DRB1gene polymorphism and ITP in children.Until now, studies main on the association between Hp and HLA gene in adults ITP, fewer studies about the association between HLA gene polymorphism and Hp infection in children ITP in domestic and foreign. and the conclusion are controversied. The pathogenesis of ITP is different between adult and children. What is the association between ITP in children and HLA gene polymorphism, whether genetic factors influence susceptibility to ITP and does it play an important role in Hp infection, and whether is Hp involved in the pathogenesis of ITP children, and whether it can be cured by bacterium eradication in ITP, all these have plagued us and urgent us to solve the problems.Object:1. To investigate the HLA-DRB1 gene polymorphism of ITP children;2. To investigate the prevalance of H. pylori infection and the association between H. pylori infection and ITP and the effect of H. pylori eradication in cITP children.3. To investigate the association between H. pylori infection and HLA-DRB1 gene polymorphisms in ITP children and the role in identify aITP and cITP.Material: 200 cases of ITP inpatients and outpatients follow-up in The First Affiliated Hospital of Zhengzhou University from July 2007?December 2008 were collected, and all were Henan Han nationality. All are in line with the diagnostic criteria revised by the ITP pediatric branch of Chinese Medical Association in 1999.97 cases were male and 103 cases were female, aged 2 months to 14 years (median age 6.8 years), and there were 118 aITP and 82 cITP of 200 cases.200 cases of healthy children from the First Affiliated Hospital of Zhengzhou University were randomly selected as controls according to the principles of group matches. Peripheral blood were collected after relatives have informed.Methods:1. H. pylori infection was assessed by the detection of H. pylori stool antigens (ELISA) and H. pylori antibodies in blood(GICA). If they are both positive,we think the patient was infected, or else not infected.2.20 H. pylori-positive ITP patients were treated by H pylori eradication therapy and glucocorticosteroid while other 20 H. pylori-positive ITP patients only treated by glucocorticosteroid.Then record the variety of platelet count in prior and post.3. PCR-SSP were used to screen HLA-DRB1*11, HLA-DRB1*14 LA-DRB1*07 HLA-DRB1*08 in ITP patients.Results:1. H. pylori was found in 54 of 118 aITP patients (45.8%),40 of 82 cITP(48.8 %), and 79 of 200 healthy children (39.5%). There were no significance difference among the three group, indicating that there was no association between Hp infection and ITP in children(X2=2.471, R=0.78, P=0.291)2. Compared with the patients only treated by glucocorticosteroid, there were no significance difference in the platelet count in cITP children who were treated by bacterial eradication and glucocorticosteroid.3. The frequencies of HLA-DRB1*14 in patients ITP was 9.5%(19/200), in healthy control was 9.0%(18/200). there were no significant difference between them (X2= 0.030. P= 0.863). The frequencies of HLA-DRB1*14 in aITP patients was 9.3%(11/118), in cITP patients was 9.8%(8/82), there were no significant difference between them(X2= 0.011. P= 0.918). The frequencies of HLA-DRB1*14 in the ITP patients with Hp-positive was 15.9%(15/94), in-the ITP patients with Hp-negative patients was 3.8%(4/106), there were no significant difference between them (X2= 8.602, P= 0.003).The frequencies of HLA-DRB1*11 in patients ITP was 14.5%(29/200),, in healthy control was 9.0%(18/200), there were no significant difference between them (X2= 2.917, P= 0.088). The frequencies of HLA-DRB1*11 in aITP patients was 9.3%(11/118), in cITP patients was 22.0%(18/82), there were no significant difference between them(X2= 6.224, P= 0.013). The frequencies of HLA-DRB1*11 in the ITP patients with Hp-positive was 22.3%(21/94), in the ITP patients with Hp-negative patients was 7.5%(8/106), there were no significant difference between them (X2= 8.794, P= 0.003).The frequencies of HLA-DRB1*07 in patients ITP was 6.5%(13/200), in healthy control was 13.5%(27/200), there were no significant difference between them (X2= 5.444, P= 0.02). The frequencies of HLA-DRB1*07 in aITP patients was 5.9%(7/118), in cITP patients was 7.3%(6/82), there were no significant difference between them(X2= 0.153, P= 0.696). The frequencies of HLA-DRB1*07 in the ITP patients with Hp-positive was 5.3%(5/94), in the ITP patients with Hp-negative patients was 7.5%(8/106), there were no significant difference between them (X2= 0.407, P= 0.524).There was no HLA-DRB1*08 positive case was detected. Conclusion:1. There is no difference in H. pylori infection rate among aITP patients, cITP patients and healthy children. Because there is no association between Hp infection and ITP in children,.then don't confirm H. pylori is the necessary etiological factor of ITP.2.The therapy of bacterial eradication+ glucocorticosteroid and glucocorticosteroid alone can increase platelet counts,but the therapy of bacterial eradication is not the specific treatment method.3.HLA-DRB1*07appears to be protective to against ITP. The HLA-DRB1*11 plays an important role in cITP.HLA-DRB1*11, HLA-DRB1*14 may be the predisposing factor of H. pylori infection in ITP patients.
Keywords/Search Tags:idiopathic thrombocytopenic purpura, children, human leukocyte antigen, polymorphism, helicobacter pylori
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