The plasma levels of soluble ST2 as a marker of gut mucosal damage in early HIV infection.
The plasma levels of soluble ST2 as a marker of gut mucosal damage in early HIV infection.
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DOI：
10.1097/qad.0000000000001105
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发表时间：
2016-06-19
期刊：
影响因子：
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通讯作者：
Montreal Primary HIV Infection, the Canadian Long-Term Non-Progressors Study Groups
中科院分区：
文献类型：
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作者：
Mehraj V;Jenabian MA;Ponte R;Lebouché B;Costiniuk C;Thomas R;Baril JG;LeBlanc R;Cox J;Tremblay C;Routy JP;Montreal Primary HIV Infection, the Canadian Long-Term Non-Progressors Study Groups
在组织屏障破坏后，白细胞介素-33（IL-33）作为“警报”释放以诱导炎症。可溶性致瘤性抑制2（sST 2）作为IL-33诱饵受体，有助于限制炎症。我们评估了早期（EHI）和慢性HIV感染（CHI）患者和精英控制者中IL-33/ST 2轴与肠道粘膜损伤标志物之间的关系。对EHI和CHI患者进行分析，以确定IL-33/sST 2随时间的变化。测定血浆中IL-33和sST 2水平。评估了sST 2水平与血浆病毒载量、CD 4+和CD 8 + T细胞计数、T细胞活化/耗竭标志物表达、肠粘膜损伤、微生物易位和炎症标志物以及犬尿氨酸/色氨酸比值之间的相关性。与未处理的CHI和未感染的对照组相比，EHI中血浆sST 2水平升高，而IL-33水平在所有组中相当。在EHI中，sST 2水平与CD 8 + T细胞计数和表达活化和耗竭标志物的T细胞百分比呈正相关，但与病毒载量或CD 4 + T细胞计数无关。血浆sST 2水平还与肠粘膜损伤、微生物易位和犬尿氨酸/色氨酸比率的血浆水平以及一些炎症标志物相关。前瞻性分析显示，早期抗逆转录病毒治疗对sST 2水平没有影响，而CHI期间开始的较长治疗时间使sST 2正常化。由于sST 2水平在EHI中升高，并且与CD 8 + T细胞计数、免疫活化和微生物易位相关，因此sST 2可作为疾病进展、肠道损伤的标志物，并可直接促进HIV发病机制。
Following tissue barrier breaches, interleukin-33 (IL-33) is released as an ‘alarmin’ to induce inflammation. Soluble suppression of tumorigenicity 2 (sST2), as an IL-33 decoy receptor, contributes to limit inflammation. We assessed the relationship between the IL-33/ST2 axis and markers of gut mucosal damage in patients with early (EHI) and chronic HIV infection (CHI) and elite controllers. Analyses on patients with EHI and CHI were conducted to determine IL-33/sST2 changes over time. IL-33 and sST2 levels were measured in plasma. Correlations between sST2 levels and plasma viral load, CD4+ and CD8+ T-cell counts, expression of T-cell activation/exhaustion markers, gut mucosal damage, microbial translocation and inflammation markers, as well as kynurenine/tryptophan ratio were assessed. Plasma sST2 levels were elevated in EHI compared with untreated CHI and uninfected controls, whereas IL-33 levels were comparable in all groups. In EHI, sST2 levels were positively correlated with the CD8+ T-cell count and the percentage of T cells expressing activation and exhaustion markers, but not with viral load or CD4+ T-cell count. Plasma sST2 levels also correlated with plasma levels of gut mucosal damage, microbial translocation and kynurenine/tryptophan ratio and for some markers of inflammation. Prospective analyses showed that early antiretroviral therapy had no impact on sST2 levels, whereas longer treatment duration initiated during CHI normalized sST2. As sST2 levels were elevated in EHI and were correlated with CD8+ T-cell count, immune activation, and microbial translocation, sST2 may serve as a marker of disease progression, gut damage and may directly contribute to HIV pathogenesis.