Transcriptomic Predictors of Paradoxical Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome.
Transcriptomic Predictors of Paradoxical Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome.
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DOI：
10.1093/ofid/ofy157
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发表时间：
2018-07
影响因子：
4.2
通讯作者：
Bohjanen PR
中科院分区：
文献类型：
--
作者：
Vlasova-St Louis I;Chang CC;Shahid S;French MA;Bohjanen PR
在开始抗逆转录病毒治疗（ART）后，约25%的人类免疫缺陷病毒（HIV）感染的隐球菌脑膜炎（CM）患者会发生隐球菌性隐球菌病相关免疫重建炎症综合征（C-IRIS），导致显著的发病率和死亡率。隐球菌脑膜炎和C-IRIS的基因组研究很少进行。我们评估了54例发生C-IRIS（27例）的HIV感染CM受试者的全血转录组学特征，并将结果与ART开始后24周内未发生神经系统恶化的对照受试者（27例）进行了比较。通过全基因组微阵列分析样品。预测筛选算法确定了干扰素驱动的抗病毒防御途径的组分的低表达，如干扰素诱导基因，以及编码粒细胞依赖性促炎反应分子的转录本的较高表达，作为随后C-IRIS的预测生物标志物。发生早期C-IRIS（在ART开始后12周内发生）的受试者的特征在于参与先天免疫的生物标志物转录物（如炎性体途径）的上调，而发生晚期C-IRIS事件（ART后12周）的受试者的特征在于T、B和自然杀伤细胞（如IFNG、IL 27、KLRB 1等）中表达的转录物的异常上调。AIM 2、BEX 1和C1 QB被确定为早期和晚期C-IRIS事件的新型生物标志物。在ART开始之前，不能建立有效的干扰素驱动的抗病毒免疫应答，伴随着全身性粒细胞促炎特征，使患者易于发展C-IRIS。虽然早期和晚期C-IRIS具有看似相似的临床表现，但它们具有不同的分子表型（如通过生物信息学分析分类的），并且由对比的炎症信号级联驱动。
Paradoxical cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS) affects ~25% of human immunodeficiency virus (HIV)-infected patients with cryptococcal meningitis (CM) after they commence antiretroviral therapy (ART) resulting in significant morbidity and mortality. Genomic studies in cryptococcal meningitis and C-IRIS are rarely performed. We assessed whole blood transcriptomic profiles in 54 HIV-infected subjects with CM who developed C-IRIS (27) and compared the results with control subjects (27) who did not experience neurological deterioration over 24 weeks after ART initiation. Samples were analyzed by whole genome microarrays. The predictor screening algorithms identified the low expression of the components of interferon-driven antiviral defense pathways, such as interferon-inducible genes, and higher expression of transcripts that encode granulocyte-dependent proinflammatory response molecules as predictive biomarkers of subsequent C-IRIS. Subjects who developed early C-IRIS (occurred within 12 weeks of ART initiation) were characterized by upregulation of biomarker transcripts involved in innate immunity such as the inflammasome pathway, whereas those with late C-IRIS events (after 12 weeks of ART) were characterized by abnormal upregulation of transcripts expressed in T, B, and natural killer cells, such as IFNG, IL27, KLRB1, and others. The AIM2, BEX1, and C1QB were identified as novel biomarkers for both early and late C-IRIS events. An inability to mount effective interferon-driven antiviral immune response, accompanied by a systemic granulocyte proinflammatory signature, prior to ART initiation, predisposes patients to the development of C-IRIS. Although early and late C-IRIS have seemingly similar clinical manifestations, they have different molecular phenotypes (as categorized by bioinformatics analysis) and are driven by contrasting inflammatory signaling cascades.
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DOI：
10.1016/s1473-3099(10)70170-5
发表时间：
2010-11
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Haddow LJ;Colebunders R;Meintjes G;Lawn SD;Elliott JH;Manabe YC;Bohjanen PR;Sungkanuparph S;Easterbrook PJ;French MA;Boulware DR;International Network for the Study of HIV-associated IRIS (INSHI)
通讯作者：
International Network for the Study of HIV-associated IRIS (INSHI)
DOI：
10.1097/qai.0b013e3181ef4963
发表时间：
2010-12-01
影响因子：
3.6
作者：
Boulware, David R.;Meya, David B.;Bohjanen, Paul R.
通讯作者：
Bohjanen, Paul R.
影响因子：
6.4
作者：
Boulware, David R.;Bonham, Shulamith C.;Bohjanen, Paul R.
通讯作者：
Bohjanen, Paul R.
影响因子：
6.4
作者：
Pappas, PG;Bustamante, B;Hsu, HH
通讯作者：
Hsu, HH
影响因子：
56.3
作者：
Mueller, Monika;Wandel, Simon;Colebunders, Robert;Attia, Suzanna;Furrer, Hansjakob;Egger, Matthias
通讯作者：
Egger, Matthias