LUIZA GUILHERME GUGLIELMI
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 - Líder
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- RHEUMATIC HEART DISEASE: MEDIATION BY COMPLEX IMMUNE EVENTS(2011) GUILHERME, L.; KOEHLER, K. F.; KALIL, J.Rheumatic fever (RF) is an autoimmune disease caused by the Gram-positive bacteria Streptococcus pyogenes following an untreated throat infection in susceptible children. Rheumatic heart disease (RHD), the most serious complication, occurs in 30-45% of RF patients and leads to chronic valvular lesions. Here, we focus on the genes that confer susceptibility for developing this disease. Molecular mimicry mediates the cross-reactions between streptococcal antigens and human proteins. Several autoantigens have been identified, including cardiac myosin epitopes, vimentin, and other intracellular proteins. In heart tissue, antigen-driven oligoclonal T cell expansions probably cause the rheumatic heart lesions. These cells are CD4(+) and produce inflammatory cytokines (TNF alpha and IFN gamma). IL-4(+) cells are found in the myocardium; however, these cells are very scarce in the valve lesions of RHD patients. IL-4 is a Th2-type cytokine and plays a regulatory role in the inflammatory response mediated by Th1 cytokines. Our findings indicate that the Th1/Th2 cytokine balance has a role in healing myocarditis while the low numbers of IL-4-producing cells in the valves probably induced the progressive and permanent valve damage.
- Rheumatic Fever: How Streptococcal Throat Infection Triggers an Autoimmune Disease(2015) GUILHERME, L.; KALIL, J.Molecular mimicry between streptococcal and human proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic fever (RF) and rheumatic heart disease (RHD). Punctual genetic polymorphisms related to both innate and adaptive immune responses are involved in the development of RF/RHD. Some adhesion molecules and chemokines facilitate the monocytes and macrophages and T and B cell infiltration to the heart-tissue. Here we presented data on molecular mimicry mediated by B and T cell responses of peripheral blood and T cell clones infiltrating heart lesions from RHD patients against streptococcal antigens and human tissue proteins. The molecular analysis of T cell recognition is assessed by the definition of heart-cross reactive antigens. Degenerate patterns of T cell receptor (TCR) recognition in which intralesional T cell clones presenting the same TCR-BVJB and AVJB and recognized different antigens are described. The production of inflammatory cytokines such as TNFa, IL-2, IL-17, IL-23 and IFNg from peripheral and heart-infiltrating mononuclear cells, suggested that Th-1 and Th-17 type cytokines are the mediators of RHD heart lesions. All the results presented here delineate the mechanisms involved in RF/RHD and can certainly be a model for other autoimmune diseases. © 2015 Elsevier B.V. All rights reserved.
conferenceObject RESTRICTED AND SKEWED TCR VB REPERTOIRE IN CHROMOSOME 22Q11.2 DELETION(2012) ARANTES, J. M.; GRASSI, M. S.; SANTOS, N. M.; GUILHERME, L.; KULIKOWSKI, L. D.; DUTRA, R. L.; WATANABE, L. A.; JACOB, C. M. A.; ZAGO, C. A.; CARNEIRO-SAMPAIO, M.Introduction: Chromosome 22q11 deletion is the most common human deletion and is found in the majority of patients with DiGeorge and velo-cardio-facial syndromes. Many patients have a mild to moderate immunodeficiency, and most have cardiac anomaly. Objective: To evaluate TCR repertoire diversity in infants with 22q11.2 deletion identified at FMUSP ward for congenital heart diseases. Methods: TCR Vβ variable chain repertoire was analyzed by the TCRBV CDR3 lenght spectratyping technique, and repertoire diversity was quantified utilizing the complexity score (CS), that represents the sum of the number of peaks for each one of the 24 BV families. 22q11.2 deletion was detected utilizing multiplex ligation-dependent probe amplification. First case report: A 9-month-old boy was identified in a survey among infants with complex congenital heart anomalies. He was born from non-consanguineous parents, weighing 2845g and presenting microcephaly, micrognathia, ocular hypertelorism and low set left ear, renal involvement, left atrial isomerism and pulmonary atresia. He also had hypocalcemia and hypoplasticthymus. He has lymphopenia=3,800 cells/mm3 (CD3=1,454 cells/mm3, CD4=888cells/mm3, CD8=537cells/mm3), thrombocytopenia=55,000, IgG+=1,285mg/dL, IgM=123mg/dL, IgA=132mg/dL. Results: The patient presented CS=49, in contrast with 2 healthy age-matched male infants with 127 and 135. Four young healthy adults presented CS between 165 and 178. The patient presented mostly olygoclonal distribution and even absence of TCRBV families, while healthy donors exhibited mainly polyclonal non-Gaussian distributions. Conclusions: The evaluation of new cases as well as the follow-up the patients will demonstrate if the repertoire diversity correlates with clinical severity.- 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.
- 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.
- Rheumatic Fever and Rheumatic Heart Disease(2017) GUILHERME, L.; SAMPAIO, R. O.; BARROS, S. Freschi de; KöHLER, K. F.; SPINA, G. S.; TARASOUTCHI, F.; KALIL, J.Rheumatic fever (RF) is the prototype of postinfectious autoimmune diseases. Similarities of structure and/or spatial conformation between Streptococcus pyogenes and human tissue proteins lead to autoimmune reactions due to molecular mimicry. The activation of T and B lymphocytes involves several genetically controlled molecules that act in both the innate and adaptive immune response. In this chapter, we describe the strains of bacteria that are more commonly involved in the development of RF worldwide as well as the genetic predisposition of diverse ethnic groups. The disease manifests in susceptible children and teenagers, usually starting as polyarthritis or Sydenham's chorea. This condition generally occurs several months after streptococcal infection. Erythema marginatum and subcutaneous nodules are rare cutaneous manifestation, and carditis is the most serious sequelae and can lead to severe valve damage and rheumatic heart disease (RHD). The immune mechanisms that lead to the diverse manifestations mentioned above are discussed. The diagnosis and treatment, particularly the revision of Jones Criteria in the era of Doppler echocardiography, as well as the perspective of vaccine development, are also presented. © 2017 Elsevier Inc. All rights reserved.
- Rheumatic fever and rheumatic heart disease(2019) GUILHERME, L.; KALIL, J.Rheumatic heart disease is a sequel of rheumatic fever that follows an untreated group A streptococcal infection of young susceptible individuals. The disease is mediated by inflammatory and autoimmune reactions. Several genes related to both innate and adaptive immune responses are involved. Human leukocytes antigens class II alleles have been associated with the disease. Both cellular and humoral immune responses are involved with the autoimmune reactions, and Th1 and Th17 inflammatory cytokines are the mediators of rheumatic heart lesions. Although humans are unique hosts for Streptococcus pyogenes infections, several studies have been done to find a suitable animal model and numerous different species (mice, rats, hamsters, rabbits, and primates). The in vitro analysis of tissue-infiltrating T cells showed their ability of recognizing several streptococcal-M protein peptides and self-antigens by molecular mimicry mechanism and demonstrated the involvement of CD4+ T cells in the pathogenesis of the disease. © 2020 Elsevier Inc. All rights reserved.
- Rheumatic Fever and Rheumatic Heart Disease(2014) GUILHERME, L.; KALIL, J.Rheumatic heart disease is a sequel of rheumatic fever that follows an untreated group A streptococcal infection of young susceptible individuals. The disease is mediated by inflammatory and autoimmune reactions. Several genes related to both innate and adaptive immune responses are involved and HLA class II alleles have also been associated with the disease. Both cellular and humoral immune responses take part in the autoimmune reactions, in which Th1 and Th17 inflammatory cytokines are mediators of the rheumatic heart lesions. Since humans are unique hosts for S. pyogenes infections, several studies have been done to find a suitable animal model in numerous different species including mice, rats, hamsters, rabbits, and primates. The in vitro analysis of heart tissue infiltrating T cells showed their ability to recognize several streptococcal-M protein peptides as well as self antigens by molecular mimicry mechanisms and demonstrated the contribution of CD4+ T cells in the pathogenesis of the disease.