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1.
《Human immunology》2022,83(1):1-9
The class I and class II Human Leucocyte Antigens (HLA) are an integral part of the host adaptive immune system against viral infections. The characterization of HLA allele frequency in the population can play an important role in determining whether HLA antigens contribute to viral susceptibility. In this regard, global efforts are currently underway to study possible correlations between HLA alleles with the occurrence and severity of SARS-CoV-2 infection. Specifically, this study examined the possible association between specific HLA alleles and susceptibility to SARS-CoV-2 in a population from the United Arab Emirates (UAE). The frequencies of HLA class I (HLA-A, -B, and -C) and HLA class II alleles (HLA-DRB1 and -DQB1); defined using Next Generation Sequencing (NGS); from 115 UAE nationals with mild, moderate, and severe SARS-CoV-2 infection are presented here. HLA alleles and supertypes were compared between hospitalized and non-hospitalized subjects. Statistical significance was observed between certain HLA alleles and supertypes and the severity of the infection. Specifically, alleles HLA-B*51:01 and HLA-A*26:01 showed a negative association (suggestive of protection), whilst genotypes HLA-A*03:01, HLA-DRB1*15:01, and supertype B44 showed a positive association (suggestive of predisposition) to COVID-19 severity. The results support the potential use of HLA testing to differentiate between patients who require specific clinical management strategies. 相似文献
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目的 利用体外细胞共培养技术模拟体内肺组织微环境,探索树突状细胞(DC)在辐射损伤细胞的抗原提呈作用。方法 60Co γ射线照射的小鼠肺上皮细胞(MLE-12)与骨髓来源DC和/或脾T淋巴细胞培养48 h,流式细胞术检测DC细胞共刺激分子CD80/86和抗原肽识别复合物MHC Ⅰ/Ⅱ表达水平,T细胞活化标志CD69/28/152表达水平以及CD4+和CD8+亚群细胞数。结果 60Co γ射线照射的MLE-12细胞凋亡率呈剂量依赖性增高,明显刺激DC细胞CD80/86和MHC II表达,但对T细胞无直接活化作用;6 Gy照射的MLE-12细胞与DC细胞和T淋巴细胞共培养48 h,T细胞CD69和CD28表达增加,CD4+和CD8+亚群细胞数均明显高于对照组,同时DC细胞出现CD86和MHCI特异性高表达。结论 辐射损伤细胞可刺激DC细胞抗原提呈功能,并对T细胞进行活化。 相似文献
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Expression of α7 nicotinic acetylcholine receptors (nAChRs) on antigen presenting cells (APCs), such as macrophages and dendritic cells, is now well established. We have shown that GTS-21, a selective α7 nAChR agonist, downregulates APC-dependent CD4+ T cell differentiation into regulatory T cells (Tregs) and effector Th1, Th2 and Th17 cells by inhibiting antigen processing, thereby interfering with antigen presentation. α7 nAChRs on Jurkat human leukemic T cells require functional T cell receptors (TCRs)/CD3 and leukocyte-specific tyrosine kinase to mediate nicotine-induced Ca2+-signaling via Ca2+ release from intracellular stores, and are insensitive to two conventional α7 nAChR antagonists, α-bungarotoxin (α-BTX) and methyllycaconitine (MLA). We investigated the effects of GTS-21, α-BTX and MLA on ovalbumin (OVA)-induced Th cytokine release from spleen cells isolated from OVA-specific TCR transgenic DO11.10 mice. We found that: (1) GTS-21 dose-dependently suppresses OVA-induced IFN-γ, IL-4 and IL-17 release, but neither α-BTX nor MLA alone affected the OVA-induced cytokine release. (2) Neither α-BTX nor MLA abolished the suppressive effects of GTS-21 on IFN-γ and IL-17 release from OVA-activated DO11.10 spleen cells. (3) GTS-21 significantly suppressed OVA-induced APC-dependent CD4+ T cell differentiation into Tregs. Neither MLA nor mecamylamine, a non-specific nAChR antagonist, abolished the suppressive effect of GTS-21 on Treg differentiation. These results suggest that α7 nAChRs on APCs involved in cytokine synthesis and T cell differentiation are insensitive to the conventional α7 nAChR antagonists, α-BTX and MLA, and that α7 nAChRs on APCs differ pharmacologically from those in neurons. 相似文献
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近年来,抗程序性细胞死亡蛋白1(PD-1)药物在转移性结直肠癌患者错配修复缺陷治疗中的成功使得该疾病的免疫治疗得以重视。然而,失配修复缺陷的结直肠癌患者仅占结肠癌患者的一部分。目前的研究重点是将免疫治疗应用到疾病的早期阶段,包括辅助一线治疗,以及检测免疫检查点抑制剂治疗的敏感性。然而,哪些患者能够从该免疫治疗中获益仍是值得商榷的问题,因为这类药物具有自身免疫毒性。PD-1的配体之一程序性细胞死亡蛋白配体1(PD-L1)作为一种检测生物标记物,其检测可以通过免疫组化来实现。但其免疫组化的检测存在一些混杂因素,包括应用不同的检测抗体、不同的免疫组化临界值、肿瘤组织的采集准备方式不同、处理过程的不同、原发与继发的活检标本、肿瘤源性或诱导的PD-L1表达,以及肿瘤与免疫细胞的染色等。目前的结果表明,免疫组化检测肿瘤过表达PD-L1的患者在接受抗PD-L1治疗时临床效果更理想,而有些低表达的肿瘤也对该治疗有所缓解,这使PD-L1的分析中存在复杂性。阐明宿主免疫系统与肿瘤微环境的机制则能够更好地解释针对PD-L1药物是否让患者受益。 相似文献
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目的:探讨曼月乐对子宫内膜异位症的治疗效果。方法:选取98例我院在2015年12月—2018年12月收治的子宫内膜异位症患者进行研究,按照入院顺序分成对照组和观察组,各49例。对照组用妈富隆治疗,观察组用曼月乐治疗,比较两组治疗情况。结果:观察组疾病治疗总有效率高于对照组,不良反应发生率低于对照组(95.92%VS79.59%,6.12%VS22.45%)(P<0.05);两组治疗前疼痛程度、子宫内膜厚度、糖类抗原125水平对比差异无统计学意义(P>0.05),观察组治疗后痛程度、子宫内膜厚度、糖类抗原125水平低于对照组[(4.98±1.09)分VS(5.72±1.32)分,(0.58±0.15)cmVS(0.68±0.16)cm,(59.34±1.81)U/mLVS(60.28±1.76)U/mL](P<0.05)。结论:在子宫内膜异位症的治疗中使用曼月乐,可提高治疗效果,缓解疼痛感,降低不良反应发生风险,推广应用价值高。 相似文献
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【目的】探讨促性腺激素释放激动剂(GnRH-α)联合宫内放置左炔诺孕酮宫内缓释系统(LNG-IUS)对子宫内膜异位症(EMT)患者术后复发、痛经程度及性激素、糖抗原125(CA125)水平的影响。【方法】选取在陕西省宝鸡市眉县人民医院拟行腹腔镜手术的EMT患者107例,按照随机数表法分为观察组(n=54)和对照组(n=53)。观察组术后给予GnRH-a治疗3个周期,并宫内放置LNG-IUS,对照组术后仅给予GnRH-α治疗3个周期。比较两组患者术前、术后不同时间的痛经程度(VAS评分)、血清CA125、雌二醇(E2)、卵泡刺激素(FSH)、促黄体生成素(LH),随访24个月,统计患者的复发情况。【结果】术后3个月、12个月及24个月,观察组患者的VAS评分均显著低于对照组(P<0.05);两组患者手术前后E2、FSH、LH水平比较差异均无统计学意义(P>0.05);两组患者术前血清CA125水平比较差异无统计学意义(P>0.05);术后12个月,观察组患者的血清CA125水平显著低于对照组(P<0.05)。术后随访24个月,观察组患者复发率为1.87%(1/53),显著低于对照组的12.96%(7/54)(P<0.05),其差异有统计学意义(χ2=4.744,P=0.029)。【结论】EMT患者术后宫内放置LNOIUS,可减少复发,降低血清CA125水平,缓解痛经,值得临床推广应用。 相似文献
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Ross M. Fasano Erin K. Meyer Jane Branscomb Mia S. White Robert W. Gibson James R. Eckman 《Transfusion medicine reviews》2019,33(1):12-23
Red blood cells (RBC) transfusion is critical in managing acute and chronic complications in sickle cell disease (SCD); however, it is complicated by RBC alloimmunization, iron overload, transfusion reactions and infection. Several reports documented an increased incidence of alloantibodies in transfused individuals with SCD, especially for Rh and Kell antigens. As a result, the National Institutes of Health Expert Panel and British Society for Haematology guidelines recommend primary matching for C/c, E/e and K antigens in addition to ABO/RhD for RBC transfusions. However, the evidence supporting these recommendations was cited as limited and understanding of alloimmunization in SCD is evolving. To examine the limitations of the evidence, we undertook a systematic review of evidence behind recommendations for limited and extended serologic and genotypic RBC antigen matching to reduce alloimmunization, autoimmunization and transfusion reactions. Searches of PubMed, Embase, Cochrane, and Web of Science databases using MeSH index and free text terms between 1976 through October 2015 and papers and captured through July 2016 through review references in papers, word of mouth, and ongoing Google Scholar and Medline Alerts identified 303 unique articles. Nineteen articles met inclusion criteria and were classified by the Oxford Centre Evidence Based levels of evidence. Strengthening the Reporting of Observational Studies in Epidemiology checklists were completed for 18 of the 19 studies. There were no prospective randomized controlled trials. Sixteen of the articles were cohort studies, two were cross-sectional studies, and one decision tree model examining costs. Low-quality evidence from observational cohort studies supports that alloimmunization prevalence can be decreased by extending serological RBC antigen matching. Transfusion reactions are generally poorly and inconsistently reported. There was no evidence reporting the effect prophylactic genotypic matching has on alloimmunization, autoimmunization or transfusion reactions. There were no studies comparing prophylactic genotypic matching to serologic matching. High-quality evidence was lacking to support clinical decision making regarding best transfusion practices. Multicenter prospective randomized clinical trials are needed to determine best strategies for reducing the rate of alloimmunization using serologic and genotypic matching. 相似文献