...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Clinical and Translational Allergy >Abs No: HLA-A*31:01 positive hypersensitive patient
【24h】

Abs No: HLA-A*31:01 positive hypersensitive patient

机译：绝对编号：HLA-A * 31：01阳性超敏患者

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

BackgroundHypersensitivity reactions to carbamazepine (CBZ) havebeen shown to be strongly associated with specifichuman leukocyte antigen (HLA) alleles, with carriers ofthe HLA alleles presenting an increased risk of developinghypersensitivity. HLA-B*15:02 was detected inalmost all cases of CBZ-induced Stevens-Johnson syndrome(SJS) in patients of Han Chinese or South-EastAsian ancestry, and its functional role in CBZ-inducedSJS has been well characterised. HLA-A*3101 is associatedwith all clinical phenotypes of CBZ-inducedhypersensitivity in Caucasian and Japanese patients.However, functional studies investigating the role ofHLA-A*31:01 in CBZ-specific T-cell responses have notbeen performed. Furthermore, CBZ-specific T-cells ofCD4+ and CD8+ phenotype are readily detectable inCaucasian patients, which is in stark contrast to thedominant CD8+ T-cell response in Han Chinese. In thisstudy we therefore investigated the HLA restriction ofCBZ-reactive T-cells from a HLA-A*31:01 positive CBZhypersensitive patient, focusing on both the CD4+ andCD8+ cells.MethodDrug-specific T-cell clones (TCC) were generated byserial dilution, and their reactivity to CBZ measured byproliferation assay. HLA restriction of TCC was assessedusing anti-HLA antibodies as well as allogeneic HLAmismatchedantigen-presenting cells (APC).ResultsActivation of CD8+ TCC could be blocked by an anti-HLA class I antibody, and also when an anti-HLA A30/A31 antibody was used. Using allogeneic HLA-A*31:01+APC and control APC expressing common HLA-Aalleles, a CBZ-specific HLA-A*31:01 dependent activationof CD8+ TCC could be demonstrated. CBZ reactivityof CD4+ TCC was restricted by HLA class II,predominantly HLA-DR and HLA-DP. CD4+ TCC proliferatedin the presence of CBZ and APC expressingHLA-DRB1*04:04, an HLA class II allele known to bepart of a common haplotype with HLA-A*31:01 in Caucasians.APCs expressing other HLA-DRB1 alleles wereunable to stimulate a response.ConclusionWe were able to characterise the individual HLA restrictionprofile of CBZ-specific CD4+ and CD8+TCC from anHLA-A*31:01+ patient. We discovered an HLA class IIallele, i.e. HLA-DRB1*04:04, to be functionally importantfor the activation of CD4+ T-cells. The strong linkagedisequilibrium between the two alleles suggests a commonhaplotype may contribute to the multi-clonal responseseen in Caucasian patients hypersensitive to CBZ.
机译：背景技术对卡马西平（CBZ）的超敏反应已显示出与特定的人类白细胞抗原（HLA）等位基因密切相关，HLA等位基因的携带者出现超敏反应的风险增加。在汉族或东南亚血统的患者中，几乎所有CBZ诱发的Stevens-Johnson综合征（SJS）病例均检测到HLA-B * 15：02，并且已明确表征了其在CBZ诱发的SJS中的功能作用。 HLA-A * 3101与白种人和日本人CBZ引起的超敏反应的所有临床表型有关。但是，尚未进行研究HLA-A * 31：01在CBZ特异性T细胞反应中的作用的功能研究。此外，在高加索人中很容易检测到CD4 +和CD8 +表型的CBZ特异性T细胞，这与汉族人主要的CD8 + T细胞反应形成鲜明对比。因此，在本研究中，我们研究了来自HLA-A * 31：01阳性CBZ超敏性患者的CBZ反应性T细胞的HLA限制，重点是CD4 +和CD8 +细胞。方法药物特异性T细胞克隆（TCC）通过血清稀释产生，并通过增殖试验测定了它们对CBZ的反应性。使用抗HLA抗体和同种HLA不匹配的抗原呈递细胞（APC）评估TCC的HLA限制性。结果CD8 + TCC的激活可以被抗HLA I类抗体阻断，也可以通过使用抗HLA A30 / A31抗体阻断用过的。使用同种异体HLA-A * 31：01 + APC和表达常见HLA-Aalleles的对照APC，可以证明CBZ特异性HLA-A * 31：01依赖CD8 + TCC的激活。 CD4 + TCC的CBZ反应性受HLA II类限制，主要是HLA-DR和HLA-DP。 CD4 + TCC在表达HLA-DRB1 * 04：04的CBZ和APC的存在下增殖，HLA-DRB1 * 04：04是白种人中已知与HLA-A * 31：01常见单倍型的一部分的HLA II类等位基因，无法表达其他HLA-DRB1等位基因。结论我们能够表征来自HLA-A * 31：01+患者的CBZ特异性CD4 +和CD8 + TCC的单个HLA限制性谱。我们发现了HLA II类等位基因，即HLA-DRB1 * 04：04，在激活CD4 + T细胞方面具有重要的功能。这两个等位基因之间的强烈连锁不平衡表明，一个共同单倍型可能有助于对CBZ过敏的高加索患者的多克隆反应。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号