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IL18 gene polymorphism and its influence on CD4+ T-cell recovery in HIV-positive patients receiving antiretroviral therapy

2019; Elsevier BV; Volume: 75; Linguagem: Inglês

10.1016/j.meegid.2019.103997

1567-7257

José Leandro Andrade‐Santos, Wlisses Henrique Veloso Carvalho‐Silva, Antônio Victor Campos Coelho, Fabrício Oliveira Souto, Sérgio Crovella, Lucas André Cavalcanti Brandão, Rafael Lima Guimarães,

Autoimmune and Inflammatory Disorders Research

Pyroptosis has been reported to be critical in human immunodeficiency virus type 1 (HIV-1) pathogenesis and acquired immunodeficiency syndrome (AIDS) progression. Even after achieving viral suppression to undetectable levels during antiretroviral therapy (ART), exacerbated CD4+ T-cell death by pyroptosis has been suggested as one of the main causes of immunological non-response. Thus, variants in genes of pyroptosis pathway were studied in individuals with poor CD4+ T-cell reconstitution under antiretroviral therapy against HIV-1.248 virologically suppressed ART-treated patients, 126 immunological non-responders (INR) and 122 immunological responders (IR) were recruited. Genotyping was performed using TaqMan probe-based realtime PCR platform. Genotype-guided flow cytometry analysis with general and recent thymic emigrant (RTE) CD4+ T-cells in pyroptosis was performed based on associated polymorphisms.Both IL18 rs187238 G allele and GG genotype were associated as protection factors against poor CD4+ T-cell recovery (OR = 0.22; 95%CI = 0.50-0.77; P = .010 and OR = 0.58; 95%CI = 0.36-0.93; P = .022, respectively). It was demonstrated a statistical association between IL18 rs187238 genotypes of ART-treated patients and death by Caspase-1 levels (P = .020). The GG genotype showed lower pyroptotic RTE CD4+ T-lymphocytes levels in the ART-treated groups comparing with CC (P = .029) and CG (P = .018) genotypes, suggesting that the G allele presence may be related to a lower IL-18 production and thus reduced dead CD4+ T-cells levels by Caspase-1.We observed that IL18 G variant allele and genotype were associated with a better immunological response, which may influence on immunological recovery of HIV-positive patients receiving antiretroviral therapy, and low Caspase-1 activity levels was observed on GG genotype when compared CC genotypes.