Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status
AbstractBackground: Advanced cirrhosis is related to alterations in immunity. We aimed to evaluate the levels of peripheral CD4+ T cells (Tregs) and plasma cytokine in patients coinfected with human immunodeficiency virus and hepatitis C virus (HIV/HCV) according to liver fibrosis stages [evaluated as liver stiffness measure (LSM)] and their linear relationship. Methods: We performed a cross-sectional study on 238 HIV/HCV-coinfected patients (119 had <12.5 kPa, 73 had 12.5–25 kPa, and 46 had >25 kPa). Peripheral T-cell subsets were phenotyped by flow cytometry, plasma biomarkers were assessed by multiplex immunoassays, and LSM was assessed by transient elastography. Results: We found HIV/HCV-coinfected patients had higher values of CD4+ Tregs (p < 0.001), memory Tregs (p ≤ 0.001), and plasma cytokine levels [IFN-γ (p ≤ 0.05) and IL-10 (p ≤ 0.01)] compared with healthy donors and HIV-monoinfected patients. In the multivariate analysis, higher LSM values were associated with reduced levels of IL-10 (adjusted arithmetic mean ratio (aAMR) = 0.83; p = 0.019), IL-2 (aAMR = 0.78; p = 0.017), TNF-α (aAMR = 0.67; p < 0.001), and IL-17A (aAMR = 0.75; p = 0.006). When we focus on HIV/HCV-coinfected patients analyzed by LSM strata, patients with ≥25 kPa had lower values of IL-2 (aAMR = 0.66; p = 0.021), TNF-α (aAMR = 0.565; p = 0.003), and IL-17A (aAMR = 0.58; p = 0.003) than patients with <12.5 kPa. Conclusion: HIV/HCV-coinfected patients showed an immunosuppressive profile compared to healthy controls and HIV-monoinfected patients. Additionally, HIV/HCV-coinfected patients with advanced cirrhosis (LSM ≥ 25 kPa) had the lowest plasma values of cytokines related to Th1 (IL-2 and TNF-α) and Th17 (IL-17A) response.
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Garcia-Broncano, P.; Medrano, L.M.; Berenguer, J.; González-García, J.; Jiménez-Sousa, M.Á.; Carrero, A.; Hontañón, V.; Guardiola, J.M.; Crespo, M.; Quereda, C.; Sanz, J.; García-Gómez, A.B.; Jimenez, J.L.; Resino, S.; GESIDA 3603b Study Group. Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status. Cells 2018, 7, 196.
Garcia-Broncano P, Medrano LM, Berenguer J, González-García J, Jiménez-Sousa MÁ, Carrero A, Hontañón V, Guardiola JM, Crespo M, Quereda C, Sanz J, García-Gómez AB, Jimenez JL, Resino S, GESIDA 3603b Study Group. Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status. Cells. 2018; 7(11):196.Chicago/Turabian Style
Garcia-Broncano, Pilar; Medrano, Luz Maria; Berenguer, Juan; González-García, Juan; Jiménez-Sousa, Mª Ángeles; Carrero, Ana; Hontañón, Victor; Guardiola, Josep M.; Crespo, Manuel; Quereda, Carmen; Sanz, José; García-Gómez, Ana Belen; Jimenez, Jose Luis; Resino, Salvador; GESIDA 3603b Study Group. 2018. "Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status." Cells 7, no. 11: 196.
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