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

Background: Highly 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. Methods: One 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. Results: The 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). 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. Conclusions: The 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.