Publications by authors named "Fernanda Silva Medeiros"

5 Publications

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Increased PD-1 Level in Severe Cervical Injury Is Associated With the Rare Programmed Cell Death 1 () rs36084323 A Allele in a Dominant Model.

Front Cell Infect Microbiol 2021 1;11:587932. Epub 2021 Jul 1.

Laboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil.

The high-risk oncogenic human papillomavirus (HPV) has developed mechanisms for evasion of the immune system, favoring the persistence of the infection. The chronic inflammation further contributes to the progression of tissue injury to cervical cancer. The programmed cell death protein (PD-1) after contacting with its ligands (PD-L1 and PD-L2) exerts an inhibitory effect on the cellular immune response, maintaining the balance between activation, tolerance, and immune cell-dependent lesion. We evaluated 295 patients exhibiting or not HPV infection, stratified according to the location (injured and adjacent non-injured areas) and severity of the lesion (benign, pre-malignant lesions). Additionally, we investigated the role of the promoter region -606G>A polymorphism (rs36084323) on the studied variables. PD-1 and expression were evaluated by immunohistochemistry and qPCR, respectively, and the polymorphism was evaluated by nucleotide sequencing. Irrespective of the severity of the lesion, PD-1 levels were increased compared to adjacent uninjured areas. Additionally, in cervical intraepithelial neoplasia (CIN) I, the presence of HPV was associated with increased ( = 0.0649), whereas in CIN III was associated with decreased ( = 0.0148) PD-1 levels, compared to the uninjured area in absence of HPV infection. The -606A allele was rare in our population (8.7%) and was not associated with the risk for development of HPV infection, cytological and histological features, and aneuploidy. In contrast, irrespective of the severity of the lesion, patients exhibiting the mutant -606A allele at single or double doses exhibited increased protein and gene expression when compared to the -606GG wild type genotype. Besides, the presence of HPV was associated with the decrease in expression and PD-1 levels in carriers of the -606 A allele presenting severe lesions, suggesting that other mediators induced during the HPV infection progression may play an additional role. This study showed that increased PD-1 levels are influenced by the -606G>A nucleotide variation, particularly in low-grade lesions, in which the A allele favors increased expression, contributing to HPV immune system evasion, and in the high-grade lesion, by decreasing tissue PD-1 levels.
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http://dx.doi.org/10.3389/fcimb.2021.587932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288189PMC
July 2021

Variation sites at the HLA-G 3' untranslated region confer differential susceptibility to HIV/HPV co-infection and aneuploidy in cervical cell.

PLoS One 2018 2;13(10):e0204679. Epub 2018 Oct 2.

Department of Immunology, Laboratory of Immunogenetics, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil.

Post-transcriptional regulatory elements associated with transcript degradation or transcript instability have been described at the 3' untranslated region (3'UTR) of the HLA-G gene. Considering that HPV infection and aneuploidy, which causes gene instability, are associated with cervical cell malignancy, as well as the fact that HIV infection and HLA-G may modulate the immune response, the present study aimed to compare the frequencies of HLA-G 3'UTR polymorphic sites (14-base pair insertion/deletion, +3142C/G, and +3187A/G) between 226 HIV+ women co-infected (n = 82) or not with HPV (n = 144) and 138 healthy women. We also evaluated the relationship between those HLA-G 3'UTR variants and aneuploidy in cervical cells. HPV types and HLA-G polymorphisms were determined by PCR and sequencing of cervical samples DNA. Aneuploidy in cervical cell was measured by flow cytometry. The HLA-G 3'UTR 14-bp ins/del was not associated with either HIV nor HIV/HPV co-infection. The +3142G allele (p = 0.049) and +3142GG genotype (p = 0.047) were overrepresented in all HIV-infected women. On the other hand, the +3187G allele (p = 0.028) and the +3187GG genotype (p = 0.026) predominated among healthy women. The +3142G (p = 0.023) and +3187A (p = 0.003) alleles were associated with predisposition to HIV infection, irrespective of the presence or not of HIV/HPV co-infection. The diplotype formed by the combination of the +3142CX (CC or CG) and +3187AA genotype conferred the highest risk for aneuploidy in cervical cell induced by HPV. The HLA-G 3'UTR +3142 and +3187 variants conferred distinct susceptibility to HIV infection and aneuploidy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204679PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168131PMC
March 2019

Association of the Polymorphism (Val16Ala) and SOD Activity with Vaso-occlusive Crisis and Acute Splenic Sequestration in Children with Sickle Cell Anemia.

Mediterr J Hematol Infect Dis 2018 21;10(1):e2018012. Epub 2018 Feb 21.

Biological Science Institute, University of Pernambuco Pernambuco, Brazil.

The SOD2 polymorphism Val16Ala T→C influences the antioxidative response. This study investigated the association of the SOD2 polymorphism and superoxide dismutase (SOD) activity with the vaso-occlusive crisis (VOC) and acute splenic sequestration (ASS) in children with sickle cell anemia (SCA). One hundred ninety-five children with SCA aged 1-9 years old were analyzed. The TC and CC genotypes were associated with lower SOD activity compared with the TT genotype (p=0.0321; p=0.0253, respectively). Furthermore, TC and CC were more frequent in patients with VOC or ASS (p=0.0285; p=0.0090, respectively). These results suggest that the SOD2 polymorphism associated with low SOD activity could be a susceptibility factor for the occurrence of VOC and ASS.
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http://dx.doi.org/10.4084/MJHID.2018.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841937PMC
February 2018

Combined genotypes of the MBL2 gene related to low mannose-binding lectin levels are associated with vaso-occlusive events in children with sickle cell anemia.

Genet Mol Biol 2017 Jul-Sep;40(3):600-603. Epub 2017 Aug 21.

Instituto de Ciências Biológicas/Faculdade de Ciências Médicas, Universidade de Pernambuco, Recife, PE, Brazil.

Sickle cell anemia (SCA) presents heterogenous clinical manifestations that cannot be explained solely by alterations to hemoglobin (Hb); other components such as endothelial adhesion, thrombosis and inflammation may be involved. The mannose-binding lectin (MBL) has an important role in innate immunity and inflammatory diseases. In this report, we describe an association between MBL2 polymorphism related to low production of serum MBL and the frequency of vasoocclusive events (FVOE) in children ≤ 5 years old with SCA (p = 0.0229; OR 5.55; CI 1.11-27.66). Further studies are needed to explore the role of low MBL2 in the pathophysiology of vasoocclusive events in SCA.
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http://dx.doi.org/10.1590/1678-4685-GMB-2016-0161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596363PMC
August 2017

Single Nucleotide Polymorphisms at +191 and +292 of Galectin-3 Gene (LGALS3) Related to Lower GAL-3 Serum Levels Are Associated with Frequent Respiratory Tract Infection and Vaso-Occlusive Crisis in Children with Sickle Cell Anemia.

PLoS One 2016 7;11(9):e0162297. Epub 2016 Sep 7.

Programa de Doutorado da Rede Nordeste de Biotecnologia, Recife, Brasil.

Introduction: Patients with sickle cell anemia (SCA) may present chronic hemolytic anemia, vaso-occlusion and respiratory tract infection (RTI) episodes. Galectin-3 (GAL-3) is a multifunctional protein involved in inflammation, apoptosis, adhesion and resistance to reactive oxygen species. Studies point to a dual role for GAL-3 as both a circulation damage-associated molecular pattern and a cell membrane associated pattern recognition receptor.

Objective: To investigate associations between the SNPs of GAL-3 gene (LGALS3) and serum levels with RTI and vaso-occlusive crisis (VOC) in children with SCA.

Materials And Methods: SNPs +191 and +292 in LGALS3 were studied using the TaqMan real-time PCR system; GAL-3 serum levels were measured by ELISA. The study included 79 children with SCA ranging from 2 to 12 years old.

Results: GAL-3 serum levels were associated with LGALS3 +191 and +292 genotypes (p <0.0001; p = 0.0169, respectively). LGALS3 +191, AA genotype was associated with low and CC with higher levels of GAL-3. For LGALS3 +292, the CC genotype was associated with lower GAL-3 and AA with higher levels. Patients with Frequency of RTI (FRTI) ≥1 presented higher frequency of +191AA (p = 0.0263) and +292AC/CC genotypes (p = 0.0320). SNP +292 was associated with Frequency of VOC (FVOC) (p = 0.0347), whereas no association was shown with SNP +191 and FVOC. However, CA/AC and AA/CC genotypes with lower GAL-3 levels showed a higher frequency in patients with FRTI ≥1 (p = 0.0170; p = 0.0138, respectively). Also, patients with FVOC ≥1 presented association with CA/AC (p = 0.0228). LGALS3 +191 and +292 combined genotypes related to low (p = 0.0263) and intermediate expression (p = 0.0245) were associated with FRTI ≥1. Lower GAL-3 serum levels were associated with FRTI ≥1 (p = 0.0426) and FVOC ≥1 (p = 0.0012).

Conclusion: Variation of GAL-3 serum levels related to SNPs at +191 and +292 may constitute a susceptibility factor for RTI and VOC frequency.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162297PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5014331PMC
August 2017
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