Ciências Farmacêuticas

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Navegando Ciências Farmacêuticas por Autor "Baruffi, Marcelo Dias"

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    Impacto das moléculas imunorregulatórias HLA-G e Galectina-1 e o fator de transcrição FOXP3 na evolução clínica de pessoas vivendo com HIV
    (Universidade Federal do Espírito Santo, 2018-10-09) Cortelette, Natalia Alves; Palomino, Gustavo Martelli; Pancoto, João Alexandre Trés; Guimarães do Bem, Daniela Amorim Melgaço; Baruffi, Marcelo Dias
    Acquired Immunodeficiency Syndrome (AIDS) is a disease caused by a chronic infection of the Human Immunodeficiency Virus (HIV). Since the beginning of the AIDS epidemic, there are more than 35 million deaths. HIV infection triggers inflammatory changes compared to those of the inflammation triggered by aging increasing the risk for age-related diseases and mortality. The association of chronic inflammation, immunosenescence and adverse effects of antiretroviral therapy (ART) provides the development of non-infectious comorbidities, typical of the elderly, in HIV patients, relatively younger, such as neurocognitive, cardiovascular, metabolic disorders, associated with the bone system and non-HIV cancers. Human leukocyte antigen (HLA)-G and Galectin-1 (Gal-1) are immunoregulatory molecules that favor the progression of HIV infection. The genetic polymorphism in the 3' UTR Insertion (Ins)/Deletion (Del) 3' untranslated region within exon 8 between the + 2961 to + 2974 sites of the HLA-G gene (rs371194629), genotypic frequencies (Del/Del) and (Ins/Del) have been associated with genotype and higher frequency (Ins/Ins) with the lowest production of this molecule. The transcription factor forkheadbox P3 (FOXP3) is related to the regulatory activity of CD4+CD25+ Tregs cells, and polymorphisms of this factor contribute to diminish or alter the functionality of these important cells in the course of HIV infection. In this study, the correlations between the 14 bp Ins/Del polymorphism of the HLA-G gene, the single nucleotide polymorphism (SNP) at the -2383 C/T position of the promoter region of the FOXP3 gene (rs3761549) and the expression of soluble forms of HLA-G (sHLA-G) and Gal1 with the comorbidities and viral load of HIV patients. Participants were genotyped using polymerase chain reaction (PCR) for HLA-G 14bp Ins/Del polymorphism and PCR with restriction fragment analysis (PCR-RFLP) for FOXP3 SNP -2338 C/T. Clinical data and viral load of the patients were collected in medical records. HLA-G and soluble Gal-1 were quantified by ELISA. HIV patients without comorbidities had a higher frequency of the Del/Del genotype of 14bp (p <0.0136; OR = 0.4431; 95% CI: 0.2333 - 0.8415) than patients with comorbidities. The allelic and genotype frequencies of FOXP3 SNP -2383 C/T were not statistically significant between patients and controls and patients with and without comorbidities. As expected, Ins/Ins patients with and without comorbidities expressed less sHLA-G than controls (p<0.0160). However, Ins/Ins patients with comorbidities expressed more Gal-1 than controls and Ins/Ins patients without comorbidities (p<0.0019). Interestingly, patients under ART, with high levels of Gal-1, with comorbidities and low sHLA-G levels, 9 had a significant positive correlation with viral load levels (r=0.9996; p=0,0173). Considering the results found in the present study, it is observed that high expression of sHLA-G and Gal1 can be associated with better or worse clinical outcome in HIV patients, respectively.