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
13 resultados
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- 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.
- Rheumatic Heart Disease: Pathogenesis and Vaccine(2018) GUILHERME, L.; BARROS, S. Freschi de; KOHLER, K. F.; SANTOS, S. R.; FERREIRA, F. Morais; SILVA, W. R.; ALENCAR, R.; POSTOL, E.; KALIL, J.Rheumatic fever (RF) and rheumatic heart disease (RHD) follow untreated S. pyogenes throat infections in children who present susceptible genes that favor the development of autoimmune reactions. In this review, we focus on the genes that confer susceptibility and on the autoimmune reactions that occur due to molecular mimicry between human-tissue proteins and streptococcal M protein. Polyarthritis is the initial manifestation, which can evolve to carditis and severe valve damage; these culminate in rheumatic heart disease (RHD) or Sydenham's chorea, which affects the central nervous system. A perspective on vaccine development to prevent the disease is also discussed.
- Analysis of the coverage capacity of the StreptInCor candidate vaccine against Streptococcus pyogenes(2014) AMICIS, Karine M. De; BARROS, Samar Freschi de; ALENCAR, Raquel E.; POSTOL, Edilberto; MARTINS, Carlo de Oliveira; ARCURI, Helen Andrade; GOULART, Cibelly; KALIL, Jorge; GUILHERME, LuizaStreptococcus pyogenes is responsible for infections as pharyngitis, sepsis, necrotizing fasciitis and streptococcal toxic shock syndrome. The M protein is the major bacterial antigen and consists of both polymorphic N-terminal portion and a conserved region. In the present study, we analyzed the in vitro ability of StreptInCor a C-terminal candidate vaccine against S. pyogenes to induce antibodies to neutralize/opsonize the most common S. pyogenes strains in Sao Paulo by examining the recognition by sera from StreptInCor immunized mice. We also evaluated the presence of cross-reactive antibodies against human heart valve tissue. Anti-StreptInCor antibodies were able to neutralize/opsonize at least 5 strains, showing that immunization with StreptInCor is effective against several S. pyogenes strains and can prevent infection and subsequent sequelae without causing autoimmune reactions.
- 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.
- In-vitro NLRP3 functional test assists the diagnosis of cryopyrin-associated periodic syndrome (CAPS) patients: A Brazilian cooperation(2022) MENDONCA, Leonardo Oliveira; TOLEDO-BARROS, Myrthes Anna Maragna; LEAL, Vinicius Nunes Cordeiro; ROA, Mariela Estefany Gislene Vera; CAMBUI, Raylane Adrielle Goncalves; TOLEDO, Eliana; BARROS, Samar Freschi; OLIVEIRA, Amanda Melato de; RIVITTI-MACHADO, Maria Cecilia; FRANCESCANTONIO, Isadora Carvalho Medeiros; GRUMACH, Anete Sevciovic; PENIDO, Norma de Oliveira; CASTRO, Fabio Fernandes Morato; KALIL, Jorge; PONTILLO, AlessandraObjective: To report our five-years experience on the use of NLRP3 inflammasome functional assays in the differential diagnosis of Brazilian patients with a clinical suspicion of CAPS. Patients and methods: The study included 9 patients belonging to 2 families (I, II) and 7 unrelated patients with a clinical suspicion of AID according to Eurofever/PRINTO classification, recruited between 2017 and 2022. The control group for the NLRP3 functional assay consisted of 10 healthy donors and for the CBA cytokines measurement of 19 healthy controls. Patients underwent clinical evaluation, genetic and functional analysis. Results: All members of the family I received the diagnosis of Muckle-Wells Syndrome (MWS), carried the NLRP3 Thr348Met variant and resulted positive for the functional assay. The 2 patients of the family II resulted negative for the mutational screening but positive for the functional assay compatible with a MWS clinical phenotype. In 2 unrelated patients with NLRP3 mutations, including a novel mutation (Gly309Val, Asp303His), a positive functional test confirmed the clinical diagnosis of NOMID. 3 unrelated MWS and 1 FCAS patients resulted negative to the genetic screening and positive for the functional test. One patient with a FCAS-like phenotype harbored the NLRP12 His304Tyr variant confirming the diagnosis of FCAS2. Conclusion: The NLRP3 inflammasome functional assay can assist the clinical diagnosis of CAPS even in patients with unknown genetic defects.
- 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.
- Rheumatic fever: From pathogenesis to vaccine perspectives(2023) GUILHERME, L.; BRANCO, C. E.; BARROS, S. F. De; KALIL, J.Rheumatic fever (RF) is considered a model of autoimmune disease due to untreated throat infection by S. pyogenes that affects children and teenagers. The autoimmune process is believed to be the basis of all of the clinical manifestations; for instance, arthritis by immune complex deposition, chorea by antibody binding to neuronal cells, skin and subcutaneous manifestations that are mediated by a delayed hypersensitivity reaction, and carditis that is caused by cross-reactive antibodies and T cells. This chapter presents an overview of the mechanisms leading to the tissue lesions, treatment, and future possibilities of a vaccine against S. pyogenes. © 2023 Elsevier Inc. All rights reserved.