Wiesner Darin L, Boulware David R
Division of Infectious Disease & International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Curr Fungal Infect Rep. 2011 Dec 1;5(4):252-261. doi: 10.1007/s12281-011-0064-8.
This review provides an overview of Cryptococcus neoformans immunology and focuses on the pathogenesis of Cryptococcus-related paradoxical immune reconstitution inflammatory syndrome (IRIS). Cryptococcal IRIS has three phases: (1) before antiretroviral therapy (ART), with a paucity of cerebrospinal fluid (CSF) inflammation and defects in antigen clearance; (2) during initial ART immune recovery, with pro-inflammatory signaling by antigen-presenting cells without an effector response; and (3) at IRIS, a cytokine storm with a predominant type-1 helper T-cell (Th(1)) interferon-gamma (IFN-γ) response. Understanding IRIS pathogenesis allows for risk stratification and customization of HIV/AIDS care. In brief, persons at high IRIS risk may benefit from enhancing microbiologic clearance by use of adjunctive agents in combination with amphotericin, prolonging initial induction therapy, and/or increasing the initial consolidation antifungal therapy dose to at least 800 mg of fluconazole daily until the 2-week CSF culture is known to be sterile. Prophylactic anti-inflammatory therapies or undue delay of ART initiation in an attempt to prevent IRIS is unwarranted and may be dangerous.
本综述概述了新型隐球菌免疫学，并着重探讨了隐球菌相关的矛盾性免疫重建炎症综合征（IRIS）的发病机制。隐球菌IRIS有三个阶段：（1）抗逆转录病毒治疗（ART）前，脑脊液（CSF）炎症反应较少且抗原清除存在缺陷；（2）初始ART免疫恢复期间，抗原呈递细胞进行促炎信号传导，但无效应反应；（3）在IRIS阶段，出现细胞因子风暴，以1型辅助性T细胞（Th(1)）的干扰素-γ（IFN-γ）反应为主。了解IRIS发病机制有助于对HIV/AIDS护理进行风险分层和个性化定制。简而言之，IRIS高风险人群可能受益于以下措施：联合使用辅助药物与两性霉素增强微生物清除，延长初始诱导治疗时间，和/或增加初始巩固抗真菌治疗剂量至每日至少800mg氟康唑，直至2周的CSF培养结果已知为无菌。预防性抗炎治疗或为预防IRIS而过度延迟ART启动是不必要的，且可能具有危险性。
