Ostrowski S R, Katzenstein T L, Pedersen M, Høyer-Hansen G, Gerstoft J, Pedersen B K, Ullum H
Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
Scand J Immunol. 2006 Jun;63(6):478-86. doi: 10.1111/j.1365-3083.2006.001768.x.
Elevated blood levels of soluble urokinase receptor (suPAR) measured by ELISA decrease in human immunodeficiency virus-1 (HIV-1)-infected patients initiating highly active antiretroviral therapy (HAART). As the suPAR ELISA measures both three- and two-domain suPAR [suPAR(I-III), suPAR(II-III)] and suPAR(I-III)-ligand complexes, the amount by which the individual suPAR forms (suPAR(I-III), suPAR(II-III) and one-domain suPAR [suPAR(I)]) decrease in plasma in HIV-1-infected patients initiating HAART is unknown. Consequently, the objective of this study was to investigate HAART-induced changes in the individual plasma suPAR forms in HIV-1-infected patients. Plasma suPAR was measured by three time-resolved fluorescence immunoassays detecting suPAR(I-III), suPAR(I-III) + suPAR(II-III) and suPAR(I) in 29 treatment-naïve HIV-1-infected patients followed annually for 5 years after initiation of HAART and in 20 age- and gender-matched healthy individuals. In addition, plasma levels of the following inflammatory markers were also investigated: soluble tumour necrosis factor receptor (sTNFr)-II, TNF-alpha, interleukins (IL)-10, IL-6, IL-4, IL-2 and interferon (IFN)-gamma. In HIV-1-infected patients, plasma suPAR(I-III), suPAR(II-III) and suPAR(I) decreased within the first treatment year (all P < 0.05) and suPAR(I-III) and suPAR(II-III) remained above normal throughout follow-up (both P < 0.05). Plasma sTNFrII, IL-6, IFN-gamma and IL-10 also decreased during HAART (all P < 0.05). In HIV-1-infected patients, sTNFrII correlated with all suPAR forms before (all P < 0.01) and after 5 years HAART (all P < 0.001), whereas sTNFrII and suPAR did not correlate in healthy individuals. Intact and cleaved plasma suPAR decreased in HIV-1-infected patients initiating HAART but remained above normal. The positive correlation with sTNFrII suggests that the individual plasma suPAR forms are linked to immune activation in HIV-1 infection.
通过酶联免疫吸附测定法（ELISA）测得，在开始高效抗逆转录病毒疗法（HAART）的人类免疫缺陷病毒1型（HIV-1）感染患者中，可溶性尿激酶受体（suPAR）的血液水平会降低。由于suPAR ELISA可检测三结构域和两结构域的suPAR [suPAR（I-III）、suPAR（II-III）]以及suPAR（I-III）-配体复合物，所以在开始HAART的HIV-1感染患者中，血浆中各个suPAR形式[suPAR（I-III）、suPAR（II-III）和单结构域suPAR [suPAR（I）]]降低的量尚不清楚。因此，本研究的目的是调查HAART对HIV-1感染患者血浆中各个suPAR形式的影响。通过三种时间分辨荧光免疫测定法检测29例未经治疗的HIV-1感染患者血浆中的suPAR（I-III）、suPAR（I-III）+ suPAR（II-III）和suPAR（I），这些患者在开始HAART后每年随访5年，并与20名年龄和性别匹配健康个体进行比较。此外，还研究了以下炎症标志物的血浆水平：可溶性肿瘤坏死因子受体（sTNFr）-II、肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-10、IL-6、IL-4、IL-2和干扰素（IFN）-γ。在HIV-1感染患者中，血浆suPAR（I-III）、suPAR（II-III）和suPAR（I）在治疗的第一年内下降（均P < 0.05），并且在整个随访期间suPAR（I-III）和suPAR（II-III）均高于正常水平（均P < 0.05）。在HAART期间，血浆sTNFrII、IL-6、IFN-γ和IL-10也下降（均P < 0.05）。在HIV-1感染患者中，sTNFrII在HAART前（均P < 0.01）和5年后（均P < 0.001）与所有suPAR形式均相关，而在健康个体中sTNFrII与suPAR不相关。开始HAART的HIV-1感染患者中，完整和裂解的血浆suPAR均下降，但仍高于正常水平。与sTNFrII的正相关表明，血浆中各个suPAR形式与HIV-1感染中的免疫激活有关。
