{"doi":"10.1111/j.1365-3083.2006.001768.x","title":"Plasma Levels of Intact and Cleaved Urokinase Receptor Decrease in HIV‐1‐Infected Patients Initiating Highly Active Antiretroviral Therapy","abstract":"<jats:title>Abstract</jats:title><jats:p>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‐α, interleukins (IL)‐10, IL‐6, IL‐4, IL‐2 and interferon (IFN)‐γ. In HIV‐1‐infected patients, plasma suPAR(I–III), suPAR(II–III) and suPAR(I) decreased within the first treatment year (all <jats:italic>P</jats:italic> &lt; 0.05) and suPAR(I–III) and suPAR(II–III) remained above normal throughout follow‐up (both <jats:italic>P</jats:italic> &lt; 0.05). Plasma sTNFrII, IL‐6, IFN‐γ and IL‐10 also decreased during HAART (all <jats:italic>P</jats:italic> &lt; 0.05). In HIV‐1‐infected patients, sTNFrII correlated with all suPAR forms before (all <jats:italic>P</jats:italic> &lt; 0.01) and after 5 years HAART (all <jats:italic>P</jats:italic> &lt; 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.</jats:p>","journal":"Scandinavian Journal of Immunology","year":2006,"id":625768,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1618516,"name":"T. L. Katzenstein","orcid":null,"position":1,"is_corresponding":false},{"id":26624,"name":"M. Pedersen","orcid":"0000-0001-5950-8018","position":2,"is_corresponding":false},{"id":1618517,"name":"G. Høyer‐Hansen","orcid":null,"position":3,"is_corresponding":false},{"id":1618518,"name":"J. Gerstoft","orcid":null,"position":4,"is_corresponding":false},{"id":1618519,"name":"B. K. Pedersen","orcid":null,"position":5,"is_corresponding":false},{"id":1618520,"name":"H. Ullum","orcid":null,"position":6,"is_corresponding":false},{"id":1618515,"name":"S. R. Ostrowski","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Plasma Levels of Intact and Cleaved Urokinase Receptor Decrease in HIV‐1‐Infected Patients Initiating Highly Active Antiretroviral Therapy","abstract":"<jats:title>Abstract</jats:title><jats:p>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‐α, interleukins (IL)‐10, IL‐6, IL‐4, IL‐2 and interferon (IFN)‐γ. In HIV‐1‐infected patients, plasma suPAR(I–III), suPAR(II–III) and suPAR(I) decreased within the first treatment year (all <jats:italic>P</jats:italic> &lt; 0.05) and suPAR(I–III) and suPAR(II–III) remained above normal throughout follow‐up (both <jats:italic>P</jats:italic> &lt; 0.05). Plasma sTNFrII, IL‐6, IFN‐γ and IL‐10 also decreased during HAART (all <jats:italic>P</jats:italic> &lt; 0.05). In HIV‐1‐infected patients, sTNFrII correlated with all suPAR forms before (all <jats:italic>P</jats:italic> &lt; 0.01) and after 5 years HAART (all <jats:italic>P</jats:italic> &lt; 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. 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