Plasma levels of intact and cleaved urokinase receptor decrease in HIV-1-infected patients initiating highly active antiretroviral therapy
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Plasma levels of intact and cleaved urokinase receptor decrease in HIV-1-infected patients initiating highly active antiretroviral therapy. / Ostrowski, S R; Katzenstein, T L; Pedersen, M; Høyer-Hansen, G; Gerstoft, J; Pedersen, Bente Klarlund; Ullum, H.
In: Scandinavian Journal of Immunology, Vol. 63, No. 6, 06.2006, p. 478-86.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Plasma levels of intact and cleaved urokinase receptor decrease in HIV-1-infected patients initiating highly active antiretroviral therapy
AU - Ostrowski, S R
AU - Katzenstein, T L
AU - Pedersen, M
AU - Høyer-Hansen, G
AU - Gerstoft, J
AU - Pedersen, Bente Klarlund
AU - Ullum, H
PY - 2006/6
Y1 - 2006/6
N2 - 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.
AB - 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.
KW - Adult
KW - Antiretroviral Therapy, Highly Active
KW - Down-Regulation
KW - Female
KW - HIV Infections
KW - HIV-1
KW - Humans
KW - Hydrolysis
KW - Male
KW - Middle Aged
KW - Prospective Studies
KW - Protein Isoforms
KW - Receptors, Cell Surface
KW - Receptors, Tumor Necrosis Factor, Type II
KW - Receptors, Urokinase Plasminogen Activator
KW - Solubility
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1111/j.1365-3083.2006.001768.x
DO - 10.1111/j.1365-3083.2006.001768.x
M3 - Journal article
C2 - 16764702
VL - 63
SP - 478
EP - 486
JO - Scandinavian Journal of Immunology, Supplement
JF - Scandinavian Journal of Immunology, Supplement
SN - 0301-6323
IS - 6
ER -
ID: 180571199