HLA与疾病课件.ppt

HLA 与 疾 病 近年免疫遗传学表明免疫与遗传有关，基因表达量的异常可以引起免疫功能的紊乱，导致免疫性疾病的发生，这为探讨免疫性疾病的发病机制开辟了新途径。 Drugs and ADRs (药物与急性皮肤反应) HLA-B*1502 Prevalent in Asia The risk of SJS/TEN is estimated to be about 1 to 6 per 10,000 new users in countries with mainly Caucasian population. The risk increases about 10 times higher among Asian Countries Variation within Asia Exists Greater than 15% of the population is reported positive in Hong Kong, Thailand, Malaysia and parts of the Philippines South Asians, including the Indians, appear to have intermediate prevalence of HLA-B*1502, averaging 2 to 4%, but higher in some groups HLA-B*1502 appears to be present at a low frequency, 1% in Japan and Korea AP-SCAR in Japan and EU A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs Of race,ethnicity,and rash: the genetics of antiepileptic drug-induced skin reactions Human leukocyte antigens and drug hypersensitivity [Pharmacogenomics] 第四届全国免疫遗传学研讨会HLA与疾病相关联的新进展 南方医科大学南方医院移植配型中心主任 肖露露 2009年4月 表5.1　与HLA- I类分子强关联的疾病 表5.2　与HLA II类分子强关联疾病（1） 表5.2　与HLA- II类分子强关联疾病（2） 近期国内临床研究进展（2008-2009） 研究趋势 1 非经典HLA基因与器官移植的关联 2 HLA与免疫系统相关疾病的研究 3 与药物副作用及个体化治疗相关的研究 HLA-DQ？ HLA-Cw？ 相关文章较少！ 单倍/体型频率与疾病相关性的文章较少！ 谢 谢！ * * 遗传多态性是药物反应中个体差异的遗传基础，通过识别特定的多态基因型与药物疗效及毒性的关系，可为个体化治疗提供依据 HLA-B*5801 SJS/TEN* Gout (痛风病) Allopurinol 别嘌呤醇(治痛风) HLA-B*1502 SJS/TEN* Epileptic seizures, neuralgia and other neural diseases 癫间,神经痛,神经疾病 Carbamazepine 痛痉宁 (镇痛,抗惊厥药) HLA Allele associated to ADR ADR Treatment(治疗) Drug(药物) SJS:Steven-Johnson综合症 TEN:毒性皮肤坏死 (Toxic Epidermal Necrolysis) SJS/TEN:1-6/10,000人(白人发病率) 亚洲地区发病率高十倍 B*1502频率: 2-4% 东南亚地区 Japan: all three AP-SCAR have HLA-B*5801 EU: 61% AP-SCAR have HLA-B*5801 51位台湾AP-SCAR患者均发现有B*5801基因 Allopurinol and HLA-B*5801 Treat chronic gout by reducing uric acid to be produced by the body 51 AP-SCAR patients, (30 HSS, 13 SJS, 5 SJS/TEN and 3 TEN 93 healthy subjects +135 tolerant patients (6 month with AP