Serum (1→3)-β-D-glucan levels in HIV-infected individuals are associated with immunosuppression, inflammation, and cardiopulmonary function.

Serum (1→3)-β-D-glucan levels in HIV-infected individuals are associated with immunosuppression, inflammation, and cardiopulmonary function.
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DOI:
10.1097/qai.0b013e318271799b
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发表时间:
2012-12-01
期刊:
Journal of acquired immune deficiency syndromes (1999)
影响因子:
--
通讯作者:
Gingo MR
Gingo MR
中科院分区:
其他
文献类型:
--
作者:
Morris A;Hillenbrand M;Finkelman M;George MP;Singh V;Kessinger C;Lucht L;Busch M;McMahon D;Weinman R;Steele C;Norris KA;Gingo MR

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HIV感染者胃肠道细菌易位与全身性炎症、HIV进展、死亡率和合并症有关。HIV感染者也易受真菌感染和定植,但真菌易位是否发生并影响HIV进展或合并症尚不清楚。用鲎试剂(Fungitell®)测定了132例hiv感染门诊患者血清(1→3)-β- d -葡聚糖。选择血浆细胞因子和外周t细胞活化标志物进行测量。进行肺功能检查和多普勒超声心动图检查。测定(1→3)-β- d -葡聚糖高(≥40pg/ml)和低(<40pg/ml)水平与hiv相关变量、炎症标志物、肺功能和肺动脉高压措施的关系。48%检测到(1→3)-β- d -葡聚糖,16.7%检测到高水平葡聚糖。高(1→3)β- d -葡聚糖的个体CD4细胞计数低于200细胞/μl的可能性更大(31.8%比8.4%,p=0.002), log10 HIV病毒水平更高(2.85比2.13对数拷贝/ml, p=0.004),使用ART的可能性更小(68.2%比90.0%,p=0.006)。血浆IL-8 (p=0.033)、TNF-α (p=0.029)、CD8+CD38+ (p=0.046)、CD8+HLA-DR+ (p=0.029)均显著升高。弥散能力异常(p=0.041)和肺动脉压异常(肺动脉收缩压p=0.006,三尖瓣反流速度p= 0.013)在高(1→3)-β- d -葡聚糖患者中更为常见。我们在hiv感染队列中发现了外周真菌细胞壁多糖的证据。我们还证明了高血清(1→3)-β- d -葡聚糖、hiv相关免疫抑制、炎症和心肺合并症之间的关联。这些结果暗示了一类新的病原体与HIV相关的微生物易位,并提示在HIV进展和合并症中的作用。
Translocation of gastrointestinal bacteria in HIV-infected individuals is associated with systemic inflammation, HIV progression, mortality, and co-morbidities. HIV-infected individuals are also susceptible to fungal infection and colonization, but whether fungal translocation occurs and influences HIV progression or co-morbidities is unknown. Serum (1→3)-β-D-glucan was measured by a Limulus Amebocyte Lysate assay (Fungitell®) in 132 HIV-infected outpatients. Selected plasma cytokines and markers of peripheral T-cell activation were measured. Pulmonary function testing and Doppler-echocardiography were performed. Relationship of high (≥40pg/ml) and low (<40pg/ml) levels of (1→3)-β-D-glucan with HIV-associated variables, inflammation markers, and pulmonary function and pulmonary hypertension measures were determined. Forty-eight percent had detectable (1→3)-β-D-glucan, and 16.7% had high levels. Individuals with high (1→3)-β-D-glucan were more likely to have CD4 counts below 200 cells/μl (31.8% vs. 8.4%, p=0.002), had higher log10 HIV viral levels (2.85 vs. 2.13 log copies/ml, p=0.004), and were less likely to use ART (68.2% vs. 90.0%, p=0.006). Plasma IL-8 (p=0.033), TNF-α (p=0.029), and CD8+CD38+ (p=0.046) andCD8+HLA-DR+ (p=0.029) were also increased with high levels. Abnormalities in diffusing capacity (p=0.041) and in pulmonary artery pressures (p=0.006 for pulmonary artery systolic pressure and 0.013 for tricuspid regurgitant velocity) were more common in those with high (1→3)-β-D-glucan. We found evidence of peripheral fungal cell wall polysaccharides in an HIV-infected cohort. We also demonstrated an association between high serum (1→3)-β-D-glucan, HIV-associated immunosuppression, inflammation, and cardiopulmonary co-morbidity. These results implicate a new class of pathogen in HIV-associated microbial translocation and suggest a role in HIV progression and co-morbidities.