José Leandro Andrade-Santos1, Wlisses Henrique Veloso Carvalho-Silva2, Antonio Victor Campos Coelho2, Fabrício Oliveira Souto2, Sergio Crovella3, Lucas André Cavalcanti Brandão4, Rafael Lima Guimarães3. 1. Department of Genetics, Federal University of Pernambuco - UFPE, Recife, Pernambuco, Brazil; Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco - UFPE, Recife, Pernambuco, Brazil. Electronic address: jlandrades19@gmail.com. 2. Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco - UFPE, Recife, Pernambuco, Brazil. 3. Department of Genetics, Federal University of Pernambuco - UFPE, Recife, Pernambuco, Brazil; Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco - UFPE, Recife, Pernambuco, Brazil. 4. Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco - UFPE, Recife, Pernambuco, Brazil; Department of Pathology, Federal University of Pernambuco - UFPE, Recife, Pernambuco, Brazil.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: Both IL18rs187238 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 IL18rs187238 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. CONCLUSION: We observed that IL18 G variant allele and genotype were associated with a better immunological response, which may influence on immunological recovery of HIV-positivepatients receiving antiretroviral therapy, and low Caspase-1 activity levels was observed on GG genotype when compared CC genotypes.
Authors: Leonn Mendes Soares Pereira; Eliane Dos Santos França; Iran Barros Costa; Erika Vanessa Oliveira Jorge; Patrícia Jeanne de Souza Mendonça Mattos; Amaury Bentes Cunha Freire; Francisco Lúzio de Paula Ramos; Talita Antonia Furtado Monteiro; Olinda Macedo; Rita Catarina Medeiros Sousa; Eduardo José Melo Dos Santos; Felipe Bonfim Freitas; Igor Brasil Costa; Antonio Carlos Rosário Vallinoto Journal: Front Immunol Date: 2022-03-16 Impact factor: 7.561