SAMAR FRESCHI DE BARROS
Índice h a partir de 2011
6
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- StreptInCor: A Candidate Vaccine Epitope against S. pyogenes Infections Induces Protection in Outbred Mice(2013) POSTOL, Edilberto; ALENCAR, Raquel; HIGA, Fabio T.; BARROS, Samar Freschi de; DEMARCHI, Lea M. F.; KALIL, Jorge; GUILHERME, LuizaInfection with Streptococcus pyogenes (S. pyogenes) can result in several diseases, particularly in children. S. pyogenes M protein is the major virulence factor, and certain regions of its N-terminus can trigger autoimmune sequelae such as rheumatic fever in susceptible individuals with untreated group A streptococcal pharyngitis. In a previous study, we utilized a large panel of human peripheral blood cells to define the C-terminal protective epitope StreptInCor (medical identity), which does not induce autoimmune reactions. We recently confirmed the results in HLA-transgenic mice. In the present study, we extended the experimental assays to outbred animals (Swiss mice). Herein, we demonstrate high titers of StreptInCor-specific antibodies, as well as appropriate T-cell immune responses. No cross-reaction to cardiac myosin was detected. Additionally, immunized Swiss mice exhibited 87% survival one month after challenge with S. pyogenes. In conclusion, the data presented herein reinforce previous results in humans and animals and further emphasize that StreptInCor could be an effective and safe vaccine for the prevention of S. pyogenes infections.
- Thymopoiesis in Pre- and Post-Hematopoietic Stem Cell Transplantation(2018) ROCHA, Luis Klaus A. da; BARROS, Samar Freschi de; BANDEIRA, Francine; BOLLINI, Alexia; TESTA, Lucia Helena de A.; SIMIONE, Anderson Joao; SOUZA, Marina de O. e; ZANETTI, Lilian P.; OLIVEIRA, Leila Cibele S. de; SANTOS, Ana Claudia F. dos; SOUZA, Mair Pedro de; COLTURADO, Vergilio Antonio R.; KALIL, Jorge; MACHADO, Clarisse M.; GUILHERME, LuizaHematopoietic stem cell transplantation (HSCT) is an important therapeutic option for some hematological diseases. However, patients who undergo HSCT acquire a state of immunodeficiency that causes significant mortality. Reconstitution of thymic function is needed to support the immune system. One way to measure thymic function is through T-cell receptor excision circle (TREC) quantification. TRECs are generated by T-cell receptor gene rearrangements during T-cell maturation in the thymus and represent a reliable marker for thymic output. In this study, we aimed to assess aging and malignant hematological diseases as two important factors that may influence thymic output before HSCT. We observed that patients before HSCT presented signal joint TREC (sjTREC) numbers lower than 606.55 copies/mu g DNA (low values) compared with healthy individuals, with an odds ratio (OR) of 12.88 [95% confidence interval (CI): 5.26-31.53; p < 0.001]. Our results showed that a group of older individuals (>= 50 years old), comprising both healthy individuals and patients, had an OR of 10.07 (95% CI: 2.80-36.20) for low sjTREC values compared with younger individuals (<= 24 years old; p < 0.001). Multiple logistic regression analysis confirmed that both older age (>= 50 years old) and malignant hematological diseases and their treatments were important and independent risk factors related to thymic function impairment (p < 0.001). The median sjTREC value for patients of all ages was significantly lower than the sjTREC median for the subgroup of older healthy individuals (>= 50 years old; p < 0.001). These data suggested that patients before HSCT and healthy individuals exhibited age-dependent thymic impairment, and that prior treatment for hematological diseases may exacerbate aging-related deterioration of natural thymic function. Furthermore, we analyzed these patients 9 months post-HSCT and compared patients who underwent autologous HSCT with those who underwent allogeneic HSCT. Both groups of patients achieved sjTREC copy numbers similar to those of healthy individuals. We did not find a close relationship between impaired thymic function prior to HSCT and worse thymic recovery after HSCT.
- A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2)(2023) MELO, Adriana; CARVALHO, Luciana Martins de; FERRIANI, Virginia Paes Leme; CAVALCANTI, Andre; APPENZELLER, Simone; OLIVEIRA, Valeria Rossato; NETO, Herberto Chong; ROSARIO, Nelson Augusto; POSWAR, Fabiano de Oliveira; GUIMARAES, Matheus Xavier; KOKRON, Cristina Maria; MAIA, Rayana Elias; SILVA, Guilherme Diogo; KELLER, Gabriel; FERREIRA, Mauricio Domingues; VASCONCELOS, Dewton Moraes; TOLEDO-BARROS, Myrthes Anna Maragna; BARROS, Samar Freschi; NETO, Nilton Salles Rosa; KRIEGER, Marta Helena; KALIL, Jorge; MENDONCA, Leonardo OliveiraIntroductionThe deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil.Patients and methodsThis is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, Sao Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected.ResultsEighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of Sao Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses.ConclusionThe low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).
- Distinct Microbial Communities in Dilated Cardiomyopathy Explanted Hearts Are Associated With Different Myocardial Rejection Outcomes(2021) PEREIRA, Jaqueline de Jesus; IKEGAMI, Renata Nishiyama; KAWAKAMI, Joyce Tiyeko; GARAVELO, Sherrira Menezes; REIS, Marcia Martins; PALOMINO, Suely Aparecida Pinheiro; MANGINI, Sandrigo; MORENO, Camila Rodrigues; BARROS, Samar Freschi de; SOUZA, Aline Rodrigues; HIGUCHI, Maria de LourdesBackgroundIdiopathic dilated cardiomyopathy (IDCM) myocardial inflammation may be associated with external triggering factors such as infectious agents. Here, we searched if moderate/severe heart transplantation rejection is related to the presence of myocardial inflammation in IDCM explanted hearts, associated with microbial communities. MethodReceptor myocardial samples from 18 explanted hearts were separated into groups according to post-transplant outcome: persistent moderate rejection (PMR; n = 6), moderate rejection (MR; n = 7) that regressed after pulse therapy, and no rejection (NR; n = 5)/light intensity rejection. Inflammation was quantified through immunohistochemistry (IHC), and infectious agents were evaluated by IHC, molecular biology, in situ hybridization technique, and transmission electron microscopy (TEM). ResultsNR presented lower numbers of macrophages, as well as B cells (p = 0.0001), and higher HLA class II expression (p <= 0.0001). PMR and MR showed higher levels of Mycoplasma pneumoniae (p = 0.003) and hepatitis B core (p = 0.0009) antigens. NR presented higher levels of parvovirus B19 (PVB19) and human herpes virus 6 (HHV6) and a positive correlation between Borrelia burgdorferi (Bb) and enterovirus genes. Molecular biology demonstrated the presence of M. pneumoniae, Bb, HHV6, and PVB19 genes in all studied groups. TEM revealed structures compatible with the cited microorganisms. ConclusionsThis initial study investigating on infectious agents and inflammation in the IDCM explanted hearts showed that the association between M. pneumoniae and hepatitis B core was associated with a worse outcome after HT, represented by MR and PMR, suggesting that different IDCM microbial communities may be contributing to post-transplant myocardial rejection.
- Underlying IPEX syndrome in a patient with idiopathic juvenile arthritis and vitiligo(2022) MENDONCA, Leonardo Oliveira; CHUSTER, Adriana Pitchon dos Reis; DORNA, Mayra Barros; BARROS, Samar Freschi; ALVES, Janaina Baptista; GONCALVES, Victor Lucas; YANG, Ariana Campos; KALIL, Jorge; TOLEDO-BARROS, Myrthes Anna Maragna; KOKRON, Cristina MariaBackground: IPEX syndrome is an X-linked inborn error of immunity clinically characterized by the triad of: enteropathy, polyendocrinopathy and eczema. However many other clinical presentations lacking the triad above described have been reported what underpin the need of careful clinical suspicion, immunological evaluation and genetic sequencing. Case presentation: Here we report a case of a Brazilian boy with severe eczema as the first and only presentation requiring cyclosporin therapy. Progressive and cumulative symptoms of arthritis and enteropathy lead to the suspicion of an inborn error of immunity. Peripheral FOXP3 expression was normal (CD127-/CD4+/CD25+/FOXP3+-396 cells-63%) and a pathogenic mutation in FOXP3 gene (c.1150G > A; p.Ala384Thr), confirmed the diagnosis of IPEX syndrome. Conclusions: IPEX syndrome should be suspected in patients presenting with severe eczema associated or not with other autoimmune/hyper inflammatory diseases in life. Our study also reinforces that FOXP3 expression by flowcytometry seems not to be a good screening method, and genetic sequencing is mandatory even in those with high suspicion and normal peripheral FOXP3 expression.
- Immunological repertoire linked to PSTPIP1-associated myeloid-related inflammatory (PAMI) syndrome(2021) MENDONCA, Leonardo Oliveira; TERRERI, Maria Teresa; OSAKU, Fabiane Mitie; BARROS, Samar Freschi; KOHLER, Karen Francine; PRADO, Alex Isidoro; BARROS, Myrthes Toledo; KALIL, Jorge; CASTRO, Fabio Fernandes MoratoBackground Mutations along PSTPIP1 gene are associated to two specific conditions, PAPA syndrome and PAMI syndrome, both autoinflammatory disorders associated to disturbances in cytoskeleton formation. Immunological aspects of PAMI syndrome has not yet been reported neither the clinical impact on therapeutical decisions. Methods Clinical data of patients records were retrospectively accessed. Genomic DNA were extracted and sequenced following standard procedures. Peripheral lymphocytes were quantified in T, B e FOXP3 phenotypes. Results We describe two related patients with PAMI syndrome harboring the usual E250K mutation. Anti-IL1 therapy could partially control the disease in the index patient. A broad spectrum of immunological effects as well as an aberrant expression of FOXP3 could be observed. Conclusions Here we report two related brazilian patients with PAMI syndromes harboring the E250K mutation in PSTPIP1, their immunological aspects and the therapeutical response to canakinumab.
- Streptococcus pyogenes strains in Sao Paulo, Brazil: molecular characterization as a basis for StreptInCor coverage capacity analysis(2015) BARROS, Samar Freschi de; AMICIS, Karine Marafigo De; ALENCAR, Raquel; SMEESTERS, Pierre Robert; TRUNKEL, Ariel; POSTOL, Edilberto; ALMEIDA JUNIOR, Joao Nobrega; ROSSI, Flavia; PIGNATARI, Antonio Carlos Campos; KALIL, Jorge; GUILHERME, LuizaBackground: Several human diseases are caused by Streptococcus pyogenes, ranging from common infections to autoimmunity. Characterization of the most prevalent strains worldwide is a useful tool for evaluating the coverage capacity of vaccines under development. In this study, a collection of S. pyogenes strains from Sao Paulo, Brazil, was analyzed to describe the diversity of strains and assess the vaccine coverage capacity of StreptInCor. Methods: Molecular epidemiology of S. pyogenes strains was performed by emm-genotyping the 229 isolates from different clinical sites, and PCR was used for superantigen profile analysis. The emm-pattern and tissue tropism for these M types were also predicted and compared based on the emm-cluster classification. Results: The strains were fit into 12 different emm-clusters, revealing a diverse phylogenetic origin and, consequently, different mechanisms of infection and escape of the host immune system. Forty-eight emm-types were distinguished in 229 samples, and the 10 most frequently observed types accounted for 69 % of all isolates, indicating a diverse profile of circulating strains comparable to other countries under development. A similar proportion of E and A-C emm-patterns were observed, whereas pattern D was less frequent, indicating that the strains of this collection primarily had a tissue tropism for the throat. In silico analysis of the coverage capacity of StreptInCor, an M protein-conserved regionally based vaccine candidate developed by our group, had a range of 94.5 % to 59.7 %, with a mean of 71.0 % identity between the vaccine antigen and the predicted amino acid sequence of the emm-types included here. Conclusions: This is the first report of S. pyogenes strain characterization in Sao Paulo, one of the largest cities in the world; thus, the strain panel described here is a representative sample for vaccine coverage capacity analysis. Our results enabled evaluation of StreptInCor candidate vaccine coverage capacity against diverse M-types, indicating that the vaccine candidate likely would induce protection against the diverse strains worldwide.
- Case Report: Expanding Clinical, Immunological and Genetic Findings in Sideroblastic Anemia With Immunodeficiency, Fevers and Development Delay (SIFD) Syndrome(2021) MENDONCA, Leonardo Oliveira; PRADO, Alex Isidoro; COSTA, Izelda Maria Carvalho; BANDEIRA, Marcia; DYER, Rafael; BARROS, Samar Freschi; KHOLER, Karen Francine; FONSECA, Luiz Augusto Marcondes; KALIL, Jorge; CASTRO, Fabio Morato; TOLEDO-BARROS, Myrthes Anna MaragnaSince the first description of the syndrome of sideroblastic anemia with immunodeficiency, fevers and development delay (SIFD), clinical pictures lacking both neurological and hematological manifestations have been reported. Moreover, prominent skin involvement, such as with relapsing erythema nodosum, is not a common finding. Up to this moment, no genotype and phenotype correlation could be done, but mild phenotypes seem to be located in the N or C part. B-cell deficiency is a hallmark of SIFD syndrome, and multiple others immunological defects have been reported, but not high levels of double negative T cells. Here we report a Brazilian patient with a novel phenotype of SFID syndrome, carrying multiple immune defects and harboring a novel mutation on TRNT1 gene.