LUANA DE MENDONCA OLIVEIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
11 resultados
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Agora exibindo 1 - 10 de 11
- Chronic activation profile of circulating CD8+T cells in Sezary syndrome(2018) TORREALBA, Marina Passos; MANFRERE, Kelly Cristina; MIYASHIRO, Denis R.; LIMA, Josenilson F.; OLIVEIRA, Luana de M.; PEREIRA, Natalli Z.; CURY-MARTINS, Jade; PEREIRA, Juliana; DUARTE, Alberto J. S.; SATO, Maria N.; SANCHES, Jose A.Sezary syndrome (SS) is a leukemic variant of cutaneous T cell lymphoma (CTCL), and the neoplastic CD4+ T cells of SS patients undergo intense clonal proliferation. Although Sezary cells have been studied extensively, studies on adaptive immunity regarding CD8+ T cells are scarce. This study aimed to investigate activation marker expression in CD8+ T cells according to the differentiation stages and IL-7/IL7Ra axis responses of patients with SS. Moreover, this study aimed to verify the soluble forms of CD38, sCD127 and IL-7 in serum. Although the SS patients of our cohort had reduced numbers of CD8+ T cells, they exhibited higher percentages of CD8+CD38+T cells, mainly effector/memory CD8+ T cells, than the control group. In contrast, down-regulated expression of the activation markers CD127/IL-7R and CD26 was found in the CD8+ T cells of SS patients. High serum levels of sCD38 and sCD127 and scarce serum levels of IL-7 were detected, emphasizing the immune activation status of SS patients. Moreover, CD8+ T cells from SS patients exhibited IL-7 unresponsiveness to STAT5 phosphorylation and Bcl-2 expression, and IL-7 priming partially restored IFN gamma production. Our findings showed a chronic activation profile of CD8+ T cells, as an attenuated cytotoxic profile and impaired IL-7 responsiveness was observed, suggesting chronic activation status of CD8+ T cells in SS patients.
- Profile of differentially expressed Toll-like receptor signaling genes in the natural killer cells of patients with Sezary syndrome(2017) MANFRERE, Kelly C. G.; TORREALBA, Marina P.; MIYASHIRO, Denis R.; PEREIRA, Natalli Z.; YOSHIKAWA, Fabio S. Y.; OLIVEIRA, Luana de M.; CURY-MARTINS, Jade; DUARTE, Alberto J. S.; SANCHES, Jose A.; SATO, Maria N.Sezary syndrome (SS), an aggressive and leukemic form of cutaneous T-cell lymphoma, usually results in shortened survival. Improving innate immunity in SS by targeting natural killer (NK) cells with Toll-like receptor (TLR) agonists could be an interesting modulatory strategy. We evaluated the NK cell populations in SS patients assessing activating and inhibitory receptors expression and profiled the differential expression of TLR signaling pathway genes in unstimulated NK cells and after TLR7/8 stimulation. We observed preserved CD56(bright) NK cells and a low percentage of CD56(dim) NK cells in the peripheral blood of SS patients compared to those in the healthy control group. Both NK cell populations showed down-modulation of NKG2C and NKG2D expression, which was associated with high serum levels of the soluble form of NKG2D ligands. In contrast, an expansion of ""memory"" CD57+ NKG2C+ NK cells and high cytomegalovirus antibody titers were detected in SS patients. Profiling of the TLR signaling genes in NK cells from SS patients showed an abundance of differentially expressed genes (DEGs) in NK cells in the unstimulated condition, with mostly up-regulation of NF kappa B/JNK p38 pathway genes, but there was down-regulation of type I (IFN-alpha/beta) and II (IFN-gamma) interferon and IL-12A. After activation of NK cells with TLR7/8 agonist, the down-regulated genes correlated with the IFN response, and IL-12 became up-regulated, together with other antitumor factors. NK cell activation with a dual agonist for TLR7 and TLR8 is able to induce the expression of IFN-gamma and type I IFN, which can improve immunity in SS patients.
- Generation of Cytotoxic T Cells and Dysfunctional CD8 T Cells in Severe COVID-19 Patients(2022) GOZZI-SILVA, Sarah Cristina; OLIVEIRA, Luana de Mendonca; ALBERCA, Ricardo Wesley; PEREIRA, Natalli Zanete; YOSHIKAWA, Fabio Seiti; PIETROBON, Anna Julia; YENDO, Tatiana Mina; ANDRADE, Milena Mary de Souza; RAMOS, Yasmim Alefe Leuzzi; BRITO, Cyro Alves; OLIVEIRA, Emily Araujo; BESERRA, Danielle Rosa; ORFALI, Raquel Leao; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCOVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The viral infection can evolve asymptomatically or can generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia based on the severity of symptoms in patients affected with COVID-19 is frequent. However, the profiles of CD4+ and CD8+ T cells regarding cytotoxicity and antiviral factor expression have not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study was to evaluate the phenotypic and functional profile of T lymphocytes in patients with moderate and severe/critical COVID-19. During the pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Notwithstanding lymphopenia, we observed an increase in the expression of CD28, a co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T lymphocytes as well as an increase in the frequency of CD4+ T cells, CD8+ T cells, and NK cells that express the immunological checkpoint protein PD-1 in patients with a severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T cells was already observed at the baseline level and scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T lymphocytes decreased the cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed by t-SNE, there were CD4+ T-cytotoxic and CD8+ T with low granzyme production, evidencing their dysfunction in severe/critical conditions. In addition, purified CD8+ T lymphocytes from patients with severe COVID-19 showed increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and, curiously, had reduced expression of TNF-alpha. The cytotoxic profile of CD4+ T cells may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T cells and CD8+ T cells in the severity of acute COVID-19 infection.
- COVID-19 Disease Course in Former Smokers, Smokers and COPD Patients(2021) ALBERCA, Ricardo Wesley; LIMA, Julia Cataldo; OLIVEIRA, Emily Araujo de; GOZZI-SILVA, Sarah Cristina; RAMOS, Yasmim Alefe Leuzzi; ANDRADE, Milena Mary de Souza; BESERRA, Danielle Rosa; OLIVEIRA, Luana de Mendonca; BRANCO, Anna Claudia Calvielli Castelo; PIETROBON, Anna Julia; PEREIRA, Natalli Zanete; TEIXEIRA, Franciane Mouradian Emidio; FERNANDES, Iara Grigoletto; DUARTE, Alberto Jose da Silva; BENARD, Gil; SATO, Maria NotomiThe severe respiratory and systemic disease named coronavirus disease-2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, the COVID-19 pandemic presents a huge social and health challenge worldwide. Many different risk factors are associated with disease severity, such as systemic arterial hypertension, diabetes mellitus, obesity, older age, and other co-infections. Other respiratory diseases such as chronic obstructive pulmonary disease (COPD) and smoking are common comorbidities worldwide. Previous investigations have identified among COVID-19 patients smokers and COPD patients, but recent investigations have questioned the higher risk among these populations. Nevertheless, previous reports failed to isolate smokers and COPD patients without other comorbidities. We performed a longitudinal evaluation of the disease course of smokers, former smokers, and COPD patients with COVID-19 without other comorbidities, from hospitalization to hospital discharge. Although no difference between groups was observed during hospital admission, smokers and COPD patients presented an increase in COVID-19-associated inflammatory markers during the disease course in comparison to non-smokers and former smokers. Our results demonstrated that smoking and COPD are risk factors for severe COVID-19 with possible implications for the ongoing pandemic.
- SARS-CoV-2 Infection and CMV Dissemination in Transplant Recipients as a Treatment for Chagas Cardiomyopathy: A Case Report(2021) GOZZI-SILVA, Sarah Cristina; BENARD, Gil; ALBERCA, Ricardo Wesley; YENDO, Tatiana Mina; TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; BESERRA, Danielle Rosa; PIETROBON, Anna Julia; OLIVEIRA, Emily Araujo de; BRANCO, Anna Claudia Calvielli Castelo; ANDRADE, Milena Mary de Souza; FERNANDES, Iara Grigoletto; PEREIRA, Natalli Zanete; RAMOS, Yasmim Alefe Leuzzi; LIMA, Julia Cataldo; PROVENCI, Bruna; MANGINI, Sandrigo; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has infected over 90 million people worldwide, therefore it is considered a pandemic. SARS-CoV-2 infection can lead to severe pneumonia, acute respiratory distress syndrome (ARDS), septic shock, and/or organ failure. Individuals receiving a heart transplantation (HT) may be at higher risk of adverse outcomes attributable to COVID-19 due to immunosuppressives, as well as concomitant infections that may also influence the prognoses. Herein, we describe the first report of two cases of HT recipients with concomitant infections by SARS-CoV-2, Trypanosoma cruzi, and cytomegalovirus (CMV) dissemination, from the first day of hospitalization due to COVID-19 in the intensive care unit (ICU) until the death of the patients.
- Platelet-Based Biomarkers for Diagnosis and Prognosis in COVID-19 Patients(2021) ALBERCA, Ricardo Wesley; SOLIS-CASTRO, Rosa Liliana; SOLIS-CASTRO, Maria Edith; CARDOSO, Fernanda; DUARTE, Alberto Jose da Silva; OLIVEIRA, Luana de Mendonca; PEREIRA, Natalli Zanete; GOZZI-SILVA, Sarah Cristina; OLIVEIRA, Emily Araujo de; AOKI, Valeria; ORFALI, Raquel Leao; BESERRA, Danielle Rosa; ANDRADE, Milena Mary de Souza; SATO, Maria NotomiCoronavirus disease 2019 (COVID-19) caused millions of deaths worldwide. COVID-19's clinical manifestations range from no symptoms to a severe acute respiratory syndrome, which can result in multiple organ failure, sepsis, and death. Severe COVID-19 patients develop pulmonary and extrapulmonary infections, with a hypercoagulable state. Several inflammatory or coagulatory biomarkers are currently used with predictive values for COVID-19 severity and prognosis. In this manuscript, we investigate if a combination of coagulatory and inflammatory biomarkers could provide a better biomarker with predictive value for COVID-19 patients, being able to distinguish between patients that would develop a moderate or severe COVID-19 and predict the disease outcome. We investigated 306 patients with COVID-19, confirmed by severe acute respiratory syndrome coronavirus 2 RNA detected in the nasopharyngeal swab, and retrospectively analyzed the laboratory data from the first day of hospitalization. In our cohort, biomarkers such as neutrophil count and neutrophil-to-lymphocyte ratio from the day of hospitalization could predict if the patient would need to be transferred to the intensive care unit but failed to identify the patients & PRIME; outcomes. The ratio between platelets and inflammatory markers such as creatinine, C-reactive protein, and urea levels is associated with patient outcomes. Finally, the platelet/neutrophil-to-lymphocyte ratio on the first day of hospitalization can be used with predictive value as a novel severity and lethality biomarker in COVID-19. These new biomarkers with predictive value could be used routinely to stratify the risk in COVID-19 patients since the first day of hospitalization.
- HIV-I INHIBITION BY IFN-I ADJUVANTS IN NEONATAL MACROPHAGES(2019) PIETROBON, Anna Julia; YOSHIKAWA, Fabio Seiti Yamada; OLIVEIRA, Luana De Mendonca; PEREIRA, Natalli Zanete; SOUZA, Tais Aparecida Matozo De; BARGIERI, Bruna Cunha De Alencar; DUARTE, Alberto Jose Da Silva; SATO, Maria Notomi
- Frequencies of CD33+CD11b+HLA-DR-CD14-CD66b+and CD33+CD11b+HLA-DR-CD14+CD66b-Cells in Peripheral Blood as Severity Immune Biomarkers in COVID-19(2020) ALBERCA, Ricardo Wesley; ANDRADE, Milena Mary de Souza; BRANCO, Anna Claudia Calvielli Castelo; PIETROBON, Anna Julia; PEREIRA, Natalli Zanete; FERNANDES, Iara Grigoletto; OLIVEIRA, Luana de Mendonca; TEIXEIRA, Franciane Mouradian Emidio; BESERRA, Danielle Rosa; OLIVEIRA, Emily Araujo de; GOZZI-SILVA, Sarah Cristina; RAMOS, Yasmim Alefe Leuzzi; BRITO, Cyro Alves de; ARNONE, Marcelo; ORFALI, Raquel Leao; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCommon clinical features of patients with Coronavirus disease-2019 (COVID-19) vary from fever, to acute severe respiratory distress syndrome. Several laboratory parameters are reported as indicators of COVID-19 severity. We hereby describe the possible novel severity biomarkers for COVID-19, CD11b+CD33+HLA-DR-CD14+ cells and CD11b+CD33+HLA-DR-CD66b+ cells.
- Proinflammatory profile of neonatal monocytes induced by microbial ligands is downmodulated by histamine(2019) BRANCO, Anna Claudia Calvielli Castelo; PEREIRA, Natalli Zanete; YOSHIKAWA, Fabio Seiti Yamada; OLIVEIRA, Luanda Mara da Silva; TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; PIETROBON, Anna Julia; TORREALBA, Marina Passos; LIMA, Josenilson Feitosa de; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiAlthough the neonatal period is characterized by relative immunological immaturity, an inflammatory response due to Toll-like receptor (TLR) activation is observed. Histamine may be one of the factors playing a role in restraining inflammation during the early stages of life. Therefore, we evaluated the responsiveness of human cord blood cells to TLR4 agonists and the immunomodulatory function of histamine in the inflammatory response. Compared with adults, mononuclear cells (MNCs) from newborns (NBs) exhibit impaired production of IFN-gamma-inducible chemokines, such as CXCL10 and CXCL9, upon lipopolysaccharide (LPS) stimulation. Notably, LPS induced a 5-fold increase in CCL2 secretion in NBs. Evaluation of the effect of histamine on LPS-induced CCL2 secretion showed an inhibitory effect in the majority of adults, whereas this effect was detectable in all NBs. Histamine receptor (HR) blockage revealed partial involvement of H1R, H2R and H4R in LPS-induced CCL2 inhibition in MNCs from both NBs and adults. As monocytes are the main type of mononuclear cell that produces CCL2, we evaluated genes related to TLR signaling upon LPS stimulation. Monocytes from NBs showed up-regulation of genes associated with JAK/STAT/NF-kappa B and IFN signaling. Some differentially expressed genes encoding proinflammatory factors were preferentially detected in LPS-activated monocytes from NBs, and markedly down-regulated by histamine. The immunomodulatory role of histamine on CCL2 and CXCL8 was detected at the transcript and protein levels. Our findings show that NBs have enhanced CCL2 responsiveness to LPS, and that histamine acts in immune homeostasis during the neonatal period to counterbalance the robustness of TLR stimulation.
- Case Report: COVID-19 and Chagas Disease in Two Coinfected Patients(2020) ALBERCA, Ricardo; YENDO, Tatiana; RAMOS, Yasmim Leuzzi; FERNANDES, Iara; OLIVEIRA, Luana; TEIXEIRA, Franciane Emidio; BESERRA, Danielle; OLIVEIRA, Emily de; GOZZI-SILVA, Sarah; ANDRADE, Milena de Souza; BRANCO, Anna Castelo; PIETROBON, Anna; PEREIRA, Natalli; BRITO, Cyro de; ORFALI, Raquel; AOKI, Valeria; DUARTE, Alberto da Silva; BENARD, Gil; SATO, MariaAmerican trypanosomiasis, also named Chagas disease (CD), is an anthropozoonosis caused by the protozoan parasite Trypanosoma cruzi. The disease affects millions of people worldwide, leading yearly to approximately 50,000 deaths. COVID-19, generated by SARS-CoV-2, can lead to lymphopenia and death. We hereby describe the first report of two patients with CD and COVID-19 coinfection, from hospitalization until patients' death.