Proinflammatory isoforms of IL-32 as novel and robust biomarkers for control failure in HIV-infected slow progressors

IL-32 的促炎亚型作为 HIV 感染慢进展者控制失败的新型可靠生物标志物

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作者:Mohamed El-Far,Pascale Kouassi,Mohamed Sylla,Yuwei Zhang,Ahmed Fouda,Thomas Fabre,Jean-Philippe Goulet,Julien van Grevenynghe,Terry Lee,Joel Singer,Marianne Harris,Jean-Guy Baril,Benoit Trottier,Petronela Ancuta,Jean-Pierre Routy,Nicole Bernard,Cécile L Tremblay    ; Investigators of the Canadian HIV+ Slow Progressor Cohort

Abstract

HIV-infected slow progressors (SP) represent a heterogeneous group of subjects who spontaneously control HIV infection without treatment for several years while showing moderate signs of disease progression. Under conditions that remain poorly understood, a subgroup of these subjects experience failure of spontaneous immunological and virological control. Here we determined the frequency of SP subjects who showed loss of HIV control within our Canadian Cohort of HIV(+) Slow Progressors and identified the proinflammatory cytokine IL-32 as a robust biomarker for control failure. Plasmatic levels of the proinflammatory isoforms of IL-32 (mainly β and γ) at earlier clinic visits positively correlated with the decline of CD4 T-cell counts, increased viral load, lower CD4/CD8 ratio and levels of inflammatory markers (sCD14 and IL-6) at later clinic visits. We present here a proof-of-concept for the use of IL-32 as a predictive biomarker for disease progression in SP subjects and identify IL-32 as a potential therapeutic target.

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