AUTHOR=Gutiérrez-Rivas Mónica , Jiménez-Sousa María Ángeles , Rallón Norma , Jiménez José Luis , Restrepo Clara , León Agathe , Montero-Alonso Marta , González-García Juan , Muñoz-Fernández María Ángeles , Benito José Miguel , Resino Salvador ,  on Behalf of ECRIS Integrated in the Spanish AIDS Research Network 

TITLE=High Plasma Levels of sTNF-R1 and CCL11 Are Related to CD4+ T-Cells Fall in Human Immunodeficiency Virus Elite Controllers With a Sustained Virologic Control

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01399

DOI=10.3389/fimmu.2018.01399

ISSN=1664-3224

ABSTRACT=<p>Our aim was to analyze the relationship between plasma inflammatory biomarkers and CD4+ T-cells evolution in human immunodeficiency virus (HIV) elite controllers (HIV-ECs) with a suppressed viremia. We carried out a retrospective study in 30 HIV-ECs classified into two groups: those showing no significant loss of CD4+ T-cells during the observation period (stable CD4+, <italic>n</italic> = 19) and those showing a significant decrease of CD4+ T-cells (decline CD4+, <italic>n</italic> = 11). Baseline plasma biomarkers were measured using a multiplex immunoassay: sTNF-R1, TRAIL, sFas (APO), sFasL, TNF-α, TNF-β, IL-8, IL-18, IL-6, IL-10, IP-10, MCP-1, MIP-1α, MIP-1β, RANTES, SDF1α, GRO-α, and CCL11. Baseline levels of sTNF-R1 and CCL11 and sTNF-R1/TNF-α ratio correlated with the slope of CD4+ T-cells (cells/μl/year) during follow-up [<italic>r</italic> = −0.370 (<italic>p</italic> = 0.043), <italic>r</italic> = −0.314 (<italic>p</italic> = 0.091), and <italic>r</italic> = −0.381 (<italic>p</italic> = 0.038); respectively]. HIV-ECs with declining CD4+ T-cells had higher baseline plasma levels of sTNF-R1 [1,500.7 (555.7; 2,060.7) pg/ml vs. 450.8 (227.9; 1,263.9) pg/ml; <italic>p</italic> = 0.018] and CCL11 [29.8 (23.5; 54.9) vs. 19.2 (17.8; 29.9) pg/ml; <italic>p</italic> = 0.041], and sTNF-R1/TNF-α ratio [84.7 (33.2; 124.2) vs. 25.9 (16.3; 75.1); <italic>p</italic> = 0.012] than HIV-1 ECs with stable CD4+ T-cells. The area under the receiver operating characteristic (ROC) curve [area under ROC curve (AUROC)] were 0.758 ± 0.093 (sTNF-R1), 0.727 ± 0.096 (CCL11), and 0.777 ± 0.087 (sTNF-R1/TNF-α). The cut-off of 75th percentile (high values) for these biomarkers had 71.4% positive predictive value and 73.9% negative predictive value for anticipating the evolution of CD4+ T-cells. In conclusion, the loss of CD4+ T-cells in HIV-ECs was associated with higher levels of two plasma inflammatory biomarkers (sTNF-R1 and CCL11), which were also reasonably accurate for the prediction of the CD4+ T-cells loss.</p>