High-dimensional immune phenotyping of blood cells by mass cytometry in patients infected with hepatitis C virus.

Abstract Objectives Chronic hepatitis C virus (HCV) infection affects the immune system. Whether elimination of HCV with direct-acting antivirals (DAA) restores immunity is unclear. We used mass cytometry to get a broad and in-depth assessment of blood cell populations of patients with chronic HCV prior to and after DAA therapy. Methods Before and 12 weeks after sustained virological response to DAA therapy (SVR12), 22 cell populations were analysed by mass cytometry in blood collected from 10 healthy controls and 20 HCV patients with (10) or without human immunodeficiency virus (HIV) (10) infection. Results HCV infection altered the frequency of 14/22 (64%) blood cell populations. At baseline, the frequencies (median [IQR]; control, HCV, HCV/HIV) of intermediate monocytes (1.2 [0.47-1.46], 1.76 [0.83-2.66], 0.78 [0.28-1.77]), non-classical monocytes (1.11 [0.49-1.26], 0.9 [0.18-0.99], 0.54 [0.28-1.77]), conventional dendritic cells type 2 (0.55 [0.35-0.59], 0.31 [0.16-0.38], 0.19 [0.11-0.36]) and CD56dim natural killer cells (8.08 [5.34-9.79], 4.72 [2.59-6.05], 3.61 [2.98-5.07]) were reduced by 35% to 65%, particularly in HCV/HIV co-infected patients. In contrast, activated double-negative T cells (0.07 [0.06-0.10], 0.10 [0.09-0.19], 0.19 [0.12-0.25]), activated CD4 T cells (0.28 [0.21-0.36], 0.56 [0.33-0.77], 0.40 [0.22-0.53]) and activated CD8 T cells (0.23 [0.14-0.42], 0.74 [0.30-1.65], 0.80 [0.58-1.16]) were increased 1.4 to 3.5 times. Upon stimulation with Toll-like receptor ligands, the expression of cytokines was up-regulated in 7/9 (78%) and 17/19 (89%) of the conditions in HCV and HCV/HIV patients, respectively. Most alterations persisted at SVR12. Conclusions Chronic HCV and HCV/HIV infections induces profound and durable perturbations of innate and adaptive immune homeostasis.