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Plasma Levels of C-Type Lectin REG3α and Gut Damage in People With Human Immunodeficiency Virus.
The Journal of Infectious Diseases ( IF 6.4 ) Pub Date : 2020-01-01 , DOI: 10.1093/infdis/jiz423
Stéphane Isnard 1, 2 , Rayoun Ramendra 1, 2, 3 , Franck P Dupuy 1, 2 , John Lin 1, 2 , Brandon Fombuena 1, 2, 3 , Nikola Kokinov 1, 2 , Ido Kema 4 , Mohammad-Ali Jenabian 3, 5, 6 , Bertrand Lebouché 1, 2 , Cecilia T Costiniuk 1, 2 , Petronela Ancuta 6, 7 , Nicole F Bernard 1, 2, 8, 9 , Michael S Silverman 10 , Peter L Lakatos 11 , Madeleine Durand 7 , Cécile Tremblay 6, 7 , Jean-Pierre Routy 1, 2, 12 ,
Affiliation  

BACKGROUND Regenerating islet-derived protein 3α (REG3α) is an antimicrobial peptide secreted by intestinal Paneth cells. Circulating REG3α has been identified as a gut damage marker in inflammatory bowel diseases. People living with human immunodeficiency virus (PWH) on antiretroviral therapy (ART) present with an abnormal intestinal landscape leading to microbial translocation, persistent inflammation, and development of non-AIDS comorbidities. Herein, we assessed REG3α as a marker of gut damage in PWH. METHODS Plasma from 169 adult PWH, including 30 elite controllers (ECs), and 30 human immunodeficiency virus (HIV)-uninfected controls were assessed. REG3α plasma levels were compared with HIV disease progression, epithelial gut damage, microbial translocation, and immune activation markers. RESULTS Cross-sectionally, REG3α levels were elevated in untreated and ART-treated PWH compared with controls. ECs also had elevated REG3α levels compared to controls. Longitudinally, REG3α levels increased in PWH without ART and decreased in those who initiated ART. REG3α levels were inversely associated with CD4 T-cell count and CD4:CD8 ratio, while positively correlated with HIV viral load in untreated participants, and with fungal product translocation and inflammatory markers in all PWH. CONCLUSIONS Plasma REG3α levels were elevated in PWH, including ECs. The gut inflammatory marker REG3α may be used to evaluate therapeutic interventions and predict non-AIDS comorbidity risks in PWH.

中文翻译:

人免疫缺陷病毒患者的血浆C型凝集素REG3α水平和肠损伤。

背景技术再生胰岛衍生蛋白3α(REG3α)是肠道Paneth细胞分泌的抗菌肽。循环中的REG3α已被确定为炎症性肠病中的肠道损伤标志物。接受抗逆转录病毒疗法(ART)感染人类免疫缺陷病毒(PWH)的人的肠道状况异常,导致微生物易位,持续性炎症和非艾滋病合并症的发展。在本文中,我们评估了REG3α作为PWH中肠道损伤的标志物。方法评估了169名成人PWH的血浆,包括30名精英控制者(EC)和30名未感染人类免疫缺陷病毒(HIV)的对照。将REG3α血浆水平与HIV疾病进展,上皮肠道损害,微生物易位和免疫激活标记进行了比较。结果从横截面来看,与对照组相比,未经治疗和接受ART治疗的PWH中的REG3α水平升高。与对照组相比,ECs的REG3α水平也升高。纵向上,无ART的PWH中REG3α水平升高,而发起ART的患者中REG3α水平降低。REG3α水平与CD4 T细胞计数和CD4:CD8比值呈负相关,而与未经治疗的参与者的HIV病毒载量以及所有PWH中的真菌产物易位和炎性标志物呈正相关。结论PWH,包括ECs,血浆REG3α水平升高。肠道炎性标记物REG3α可用于评估PWH中的治疗干预措施和预测非艾滋病合并症的风险。不进行抗逆转录病毒治疗的PWH中REG3α水平升高,而开始抗逆转录病毒治疗的人群中REG3α水平降低。REG3α水平与CD4 T细胞计数和CD4:CD8比值呈负相关,而与未经治疗的参与者的HIV病毒载量以及所有PWH中的真菌产物易位和炎性标志物呈正相关。结论PWH,包括ECs,血浆REG3α水平升高。肠道炎性标记物REG3α可用于评估PWH中的治疗干预措施和预测非艾滋病合并症的风险。不进行抗逆转录病毒治疗的PWH中REG3α水平升高,而开始抗逆转录病毒治疗的人群中REG3α水平降低。REG3α水平与CD4 T细胞计数和CD4:CD8比值呈负相关,而与未经治疗的参与者的HIV病毒载量以及所有PWH中的真菌产物易位和炎性标志物呈正相关。结论PWH,包括ECs,血浆REG3α水平升高。肠道炎性标记物REG3α可用于评估PWH中的治疗干预措施和预测非艾滋病合并症的风险。
更新日期:2019-12-17
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