3 years ago

Serum suppression of tumorigenicity 2 level is an independent predictor of all-cause mortality in HIV-infected patients

Serum suppression of tumorigenicity 2 level is an independent predictor of all-cause mortality in HIV-infected patients
Le Marec, Fabien, Duffau, Pierre, Dabis, François, Thiébaut, Rodolphe, Bonnet, Fabrice, Foucat, Emile, Wittkop, Linda, Dupon, Michel, Lazaro, Estibaliz, Hue, Sophie, for the ANRS CO3 Aquitaine Cohort, Lelièvre, Jean-Daniel, Lévy, Yves, Pellegrin, Isabelle, Surenaud, Mathieu, Lacabaratz, Christine
Objective:To evaluate the predictive value of soluble suppression of tumorigenicity 2 (sST2), a decoy receptor of IL-33 involved in several inflammatory and immune diseases, for death in HIV infection. Design:Patients enrolled in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients, who had a plasma sample available in the biobank were systematically eligible. Methods:sST2, soluble CD14 (sCD14) and IL-6 were measured using Luminex multiplex bead-based technology (R&D Systems) and a Bio-Plex 200 instrument (BioRad). Predictive capacities of sST2, sCD14, IL-6 and of the Veterans Aging Cohort Study clinical score at baseline on overall mortality were compared using multivariable Cox proportional hazards models. Results:During a median follow-up of 7.2 years [interquartile range (IQR): 6.0; 7.9], 93 deaths from all causes (incidence rate 9.9 per 1000 patient-years; 95% confidence interval 7.9–11.9) were reported in 1414 patients. The median sST2 baseline concentration was 22.9 ng/ml (IQR: 17.7; 30.3) and was higher (30.8 ng/ml, IQR: 21.5; 42.1) in patients who died as compared with those who stayed alive (22.6 ng/ml; IQR: 17.5; 29.6) (P < 10−4). An increased risk of death of 21% for a concentration 10.0 ng/ml higher of sST2 remained after adjustment for sCD14, IL-6 and Veterans Aging Cohort Study score (adjusted hazard ratio: 1.21; P < 10−4). The predictive capacity of sST2 was confirmed in a validation cohort (n = 386, 31 deaths) with an improved area c-index from 0.804 without sST2 to 0.811 with sST2. Conclusion:sST2 is a new valuable biomarker to evaluate the risk of all-cause mortality in HIV disease.
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