High plasma levels of intact and cleaved soluble urokinase receptor reflect immune activation and are independent predictors of mortality in HIV-1-infected patients.
BACKGROUND
High blood levels of soluble urokinase receptor (suPAR) measured by enzyme-linked immunoassay (ELISA) (bulk measurement of 3-domain and 2-domain suPAR [suPAR(I-III), suPAR(II-III)], and suPAR(I-III) ligand complexes) strongly predict mortality in HIV-1-infected patients. This study investigated plasma levels of suPAR(I-III), suPAR(II-III), and 1-domain suPAR [suPAR(I)] and their predictive value for survival in HIV patients.


METHODS
Plasma suPAR was measured by ELISA and 3 different time-resolved fluorescence immunoassays detecting suPAR(I-III), suPAR(I-III) plus suPAR(II-III), and suPAR(I) in 99 HIV patients and 59 healthy individuals.


RESULTS
Plasma suPAR(I-III), suPAR(II-III), and suPAR(I) were increased in HIV patients and increased with HIV disease progression (P < 0.001 for all). In multivariate linear regression analysis, soluble immune activation markers and hemoglobin were independent predictors of plasma suPAR in HIV patients, whereas the neutrophil concentration was the only independent predictor of plasma suPAR in controls. In univariate Cox analysis, higher levels of suPAR(I-III), suPAR(II-III), and suPAR(I) predicted increased mortality risk (P < 0.001 for all). In multivariate Cox analysis adjusting for CD4+ count, HIV RNA, beta2-microglobulin, hemoglobin and clinical stage, higher levels of suPAR(I-III) and suPAR(II-III) were independent predictors of increased mortality risk (P < 0.05 for both), whereas suPAR(I) was not.


CONCLUSIONS
Plasma levels of different suPAR forms are increased and associated with immune activation in HIV patients, and suPAR(I-III) and suPAR(II-III) are independent predictors of mortality in these patients.
Ostrowski
Sisse Rye
SR
Department of Infectious Diseases, Rigshospitalet, Copenhagen, DK-2100 Denmark. sro@dadlnet.dk
Piironen
Timo
T
Høyer-Hansen
Gunilla
G
Gerstoft
Jan
J
Pedersen
Bente Klarlund
BK
Ullum
Henrik
H
D000328:Adult; D000704:Analysis of Variance; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000401:mortality*; D006801:Humans; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012367:RNA, Viral / Q000097:blood; D011956:Receptors, Cell Surface / Q000097:blood*; D055293:Receptors, Urokinase Plasminogen Activator; D012016:Reference Values; D012044:Regression Analysis; D016019:Survival Analysis; D019562:Viral Load
D015703:Antigens, CD; D015415:Biomarkers; C524898:PLAUR protein, human; D012367:RNA, Viral; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator