Pyroptosis associated with immune reconstruction failure in HIV-1- infected patients receiving antiretroviral therapy: a cross-sectional study

Abstract

Background: Highly active anti-retroviral therapy (HAART) can successfully suppress human immunodeficiency virus (HIV) viral replication and reconstruct immune function reconstruction in HIV-1-infected patients. However, about 15-30% of HIV-1-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-1- infected patients. The study aims to explore the association between the expression of pyroptosis in peripheral blood and immune function reconstruction in HIV-1- infected patients.

Methods: One hundred thirty-five HIV-1-infected patients including immunological non-responders (INR) group, immunological responders (IR) group and normal immune function control (NC) group were analyzed. The expression of GSDMD and Caspase-1 in peripheral blood of HIV-1-infected patients were measured by qPCR. The concentrations of GSDMD, Caspase-1, 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). There was no significant difference in the 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 7.051, 95% CI 1.115-44.592, P = 0.038), high level of expression of Caspase-1mRNA (aOR 2.803, 95% CI 1.065-7.377, P = 0.037) and IL-18 cytokine (aOR 10.131, 95% CI 1.616-63.505, P = 0.013) had significant poor CD4⁺ T cell recovery.

Conclusions: The baseline CD4⁺ T cell counts less than 100 cells/μL, high relative expression of Caspase-1 mRNA, and high expression of IL-18 cytokine are associated factors that affect the reconstruction of immune function.

Keywords: Caspase-1; Gasdermin D (GSDMD); Human immunodeficiency virus (HIV); Immune reconstitution; Pyroptosis.