Caspase-1 -dependent pyroptosis are associated with immune reconstruction failure in HIV-positive patients receiving antiretroviral therapy: a cross-sectional study

Abstract

Abstract BackgroundHighly Active Anti-Retroviral Therapy (HAART) can successfully suppress HIV-1 viral replication and reconstruct immune function reconstruction in HIV infected patients. However, about 15-30 % of HIV infected patients still fail to recover their CD4+T cell counts after HAART treatment, which means immune reconstruction failure. Pyroptosis plays an important role in the death of CD4+T cells in HIV infected patients. The study aims to explore the association between the expression of pyroptosis in peripheral blood and immune function reconstruction in HIV infected patients.MethodsOne hundred fifty-three HIV-infected patients including immunological nonresponders group (INR), immunological responders group (IR) and normal immune function control group (NC) were analyzed. The expression of GSDMD and Caspase-1 in peripheral blood of HIV infected patients were measured by qPCR. The concentrations of IL-1β and IL-18 in the peripheral serum were quantified by ELISA. The associations between the expression of pyroptosis in peripheral blood and immune function reconstruction were analyzed using multivariate logistic models.ResultsThe relative expression of GSDMD mRNA and caspase-1 mRNA in peripheral blood, as well as the expression of IL-18 cytokine in the INR, were significantly higher than those in the IR and NC(P<0.05). There was no significant difference in expression of IL-1β cytokine (P>0.05). Multivariate logistic analysis showed that the patients with baseline CD4+T cell counts less than 100 cells/μL (aOR=5.913, 95%CI=1.061-32.958, P=0.043), high level of expression of Caspase-1mRNA (aOR=2.833,95%CI=1.127-7.126, P=0.027) and IL-18 cytokine (aOR=8.569, 95%CI=1.661-44.195, P=0.010) had significant poor CD4+T cell recovery. ConclusionsThe pyroptosis was overactivated in peripheral blood in HIV infected patients with immune reconstitution failure. The baseline CD4+T cell count less than 100 cells/μL, high relative expression of Caspase-1 mRNA, and high expression of IL-18 cytokine are independent risk factors that affect the reconstruction of immune function.