认识免疫重建炎症综合征

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1、关于认识免疫重建炎症综合征第一页，共31页幻灯片 A 35-year-old male with an 8-year history of AIDS presented with a 3-day history of recurrent frontal headaches, subjective fever and alter edmental status. He had a history of non-adherence to medications, but he had resumed antiretroviral drugs for about 10 weeks. Four wee

2、ks prior to presentation to our hospital, he had been diagnosed with cryptococcal meningitis (CM) in an outside hospital and had received a 7 day course of intravenous amphotericin B (lipid complex preparation). This was discontinued due to progressive acute kidney injury and he was subsequently pla

3、ced on high dose (800 mg) oral fluconazole (FLU) daily.Case ReportInfectious Disease Reports 2014; volume 6:5576第二页，共31页幻灯片Case ReportInfectious Disease Reports 2014; volume 6:5576第三页，共31页幻灯片Case ReportHe was readmitted to the hospital 5 weeks later with recurrent headaches and fevers.MRI of his bra

4、in showed no change.Infectious Disease Reports 2014; volume 6:5576第四页，共31页幻灯片HIV infection is characterized by a gradual reduction in the counts of CD4+ lymphocytes发现第五页，共31页幻灯片命名 起初： 免疫修复疾病(im une reeonstitutiodisease，IRD) 免疫重建病(immune reconstitution syndrome，IRS)鉴于宿主的炎性反应在发病中的重要作用, DeSimone 等首次提出免

5、疫重建炎性综合征。 (immune reconstitution inflammation syndrome，IRIS)第六页，共31页幻灯片 分枝杆菌引起的淋巴结病、结核病的异常表现 进展性多灶性脑白质病的恶化 耶氏肺孢子菌肺炎 弓形虫病的复发 巨细胞病毒性视网膜炎 病毒性肝炎 有些则可能表现为自身免疫性疾病临床表现 根据涉及的感染性或非感染性因子的不同而不同IRIS which may manifest as a newly identified opportunistic infection (OI) in previously asymptomatic individuals (unm

6、asking IRIS) or with paradoxical clinical worsening of a known OI (paradoxical IRIS).第七页，共31页幻灯片IRIS的危害 部分患者不能耐受现有的治疗或对ART药物的作用产生怀疑自行停止ART ； 服药的依从性降低，导致诱发HIV耐药变异的产生与传播，影响ART的远期治疗效果和未来治疗的选择； 增加住院率，降低患者生活质量，提高艾滋病防治工作成本；IRIS的表现常被误判为抗OI病原体治疗无效所引起的一系列表现，导致对其治疗方案的不适当调整。少数患者因IRIS死亡 ； 影响患者的远期免疫功能重建，研究表明部分发生

7、IRIS的患者，ART 3-4年后CD 细胞的恢复仍受到影响 。Int J Infect Dis，2011;15:e408-e14.Med Mycol Case Rep，2014;5:16-9.Curr Infect Dis Rep 2013;15:583-93.第八页，共31页幻灯片艾滋病患者在接受ART后6个月内IRIS的发病率： 欧美发达国家为10 15。 资源有限的发展中国家为20 25。 绝大多数发生于治疗的前3个月 。IRIS的发病率Jpn J Idea Dis，2008，61：205-9.AIDS，2008，22：601-10.第九页，共31页幻灯片体液免疫相关的辅助性T细胞在介

8、导机体与外源性抗原的免疫反应中起重要作用。同源性配体激发Th0细胞(初始CD4+T细胞)在不同细胞因子的作用下进行分化。 Th1细胞能分泌干扰素(interferon ，IFN-)，引起前炎症反应。Th2细胞能分泌抗炎和免疫抑制性细胞因子如interleukin 10，IL-10)。 Th3细胞能分泌转化生长因子 (transforming growth factor ，TGF- )。Th2细胞能抑制Th1细胞的转化及其细胞功能。一个正常功能的免疫系统是基于Th1和Th2功能的平衡。IRIS的发病机制第十页，共31页幻灯片Schematic diagram demonstrating the

9、proposed pathogenesis of PR/IRIS in relation to time, mycobacterial load, and the immune response. The lower panel shows pathogenesis in the non-PR/IRIS context, wherein mycobacterial burden and the immune response/inflammation are closely coupled temporally, and where inflammation (and clinical fea

10、tures) resolves in tandem with mycobacterial burden when treatment is initiated. The upper panel shows pathogenesis in the context of PR/IRIS, wherein the baseline immunocompromised phenotype means there is excessive mycobacterial outgrowth in a poorly inflamed environment. When treatment is initiat

11、ed that reverses immunocompromise, an excessively exuberant inflammatory response develops (PR/IRIS) with symptoms temporally distinct from those arising as part of the original untreated infection. L.C.K. Bell et al. / International Journal of Infectious Diseases 32 (2015) 3945 43第十一页，共31页幻灯片IRIS的发