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Blood, 15 December 2000, Vol. 96, No. 13, pp. 4091-4095
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Serum level of soluble urokinase-type plasminogen activator
receptor is a strong and independent predictor of survival in human
immunodeficiency virus infection
Nicolai Sidenius,
Cornelis F. M. Sier,
Henrik Ullum,
Bente Klarlund Pedersen,
Alessandro Cozzi Lepri,
Francesco Blasi, and
Jesper Eugen-Olsen
From the Department of Molecular Pathology and
Medicine, Molecular Genetics Unit, DIBIT, San Raffaele Scientific
Institute, Milan, Italy; the Department of Infectious Diseases,
Rigshospitalet, Copenhagen; the Department of Infectious Diseases and
Clinical Research Unit, Hvidovre Hospital, Denmark; and the Royal Free
Centre for HIV Medicine and the Department of Primary Care and
Population Sciences, Royal Free and University College Medical School,
University College London, London, United Kingdom.
Human immunodeficiency virus-1 (HIV-1) infection has been shown to
result in up-regulation of the urokinase-type plasminogen activator
receptor (uPAR/CD87) on leukocytes in vitro and in vivo. The objective of this study was to investigate whether this
up-regulation is paralleled by higher serum levels of soluble uPAR
(suPAR) in patients with advanced HIV-1 disease and whether the serum
level of suPAR is predictive of clinical outcome. Using an
enzyme-linked immunosorbent assay, the level of suPAR was measured
retrospectively in serum samples from 314 patients with HIV-1
infection. By Kaplan-Meier and Cox regression analyses, the serum suPAR
levels were correlated to survival with AIDS-related death as the end
point. High levels of serum suPAR (greater than median) were associated
with poor overall survival, and Kaplan-Meier analysis on patients
stratified by suPAR level demonstrated a continuous increase in
mortality rates with higher suPAR levels. After adjustment for accepted prognostic markers including Centers for Disease Control and
Prevention-defined clinical stages, CD4 counts, viral load,
 2-microglobulin, and agethe prognostic strength of suPAR remained
highly significant, indicating that the serum suPAR level is a novel,
strong, and independent predictor of survival in HIV-1 infection. This
report is the first to demonstrate an important association between the plasminogen activator system and disease progression in HIV-1 infection.
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