Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection

• Published in: Blood 2000-12, Vol.96 (13), p.4091-4095
• Main Authors: Sidenius, Nicolai, Sier, Cornelis F.M., Ullum, Henrik, Pedersen, Bente Klarlund, Lepri, Alessandro Cozzi, Blasi, Francesco, Eugen-Olsen, Jesper
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antiretroviral Therapy, Highly Active; Biological and medical sciences; Cohort Studies; Denmark - epidemiology; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - mortality; HIV-1; Human viral diseases; Humans; Infectious diseases; Life Tables; Male; Medical sciences; Middle Aged; Prognosis; Proportional Hazards Models; Receptors, Cell Surface - blood; Receptors, Urokinase Plasminogen Activator; Retrospective Studies; Severity of Illness Index; Solubility; Survival Analysis; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V96.13.4091

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, β2-microglobulin, and age—the 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.