title: Plasma levels of intact and cleaved urokinase receptor decrease in HIV-1-infected patients initiating highly active antiretroviral therapy.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark. sro@dadlnet.dk
authors.forename: S R
authors.initials: SR
authors.lastname: Ostrowski
authors.forename: T L
authors.initials: TL
authors.lastname: Katzenstein
authors.forename: M
authors.initials: M
authors.lastname: Pedersen
authors.forename: G
authors.initials: G
authors.lastname: Høyer-Hansen
authors.forename: J
authors.initials: J
authors.lastname: Gerstoft
authors.forename: B K
authors.initials: BK
authors.lastname: Pedersen
authors.forename: H
authors.initials: H
authors.lastname: Ullum
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020033:Protein Isoforms / Q000097:blood; D011956:Receptors, Cell Surface / Q000097:blood* / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D012995:Solubility
chemical_list: C524898:PLAUR protein, human; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D047889:Receptors, Tumor Necrosis Factor, Type II; D055293:Receptors, Urokinase Plasminogen Activator