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
9 resultados
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- 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.
- 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.
- 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.
- Ficolin-3 in rheumatic fever and rheumatic heart disease(2021) CATARINO, Sandra Jeremias; ANDRADE, Fabiana Antunes; BAVIA, Lorena; GUILHERME, Luiza; MESSIAS-REASON, Iara JoseRheumatic fever (RF) and chronic rheumatic heart disease (RHD) are complications of oropharyngeal infection caused by Streptococcus pyogenes. Despite the importance of the complement system against infections and autoimmunity diseases, studies on the role of the lectin pathway in RF and RHD are scarce. Thus, our aim was to evaluate the association of ficolin-3 serum levels, FCN3 polymorphisms and haplotypes with the susceptibility to RF and RHD. We investigated 179 patients with a history of RF (126 RHD and 53 RF only) and 170 healthy blood donors as control group. Ficolin-3 serum concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Three FCN3 single nucleotide polymorphisms (SNPs rs532781899, rs28362807 and rs4494157) were genotyped through the sequence-specific PCR method. Lower ficolin-3 serum levels were observed in RF patients when compared to controls (12.81 mu g/mL vs. 18.14 mu g/mL respectively, p < 0.0001, OR 1.22 [1.12-1.34]), and in RHD in comparison to RF only (RFo) (12.72 mu g/mL vs. 14.29 mu g/mL respectively, p = 0.016, OR 1.38 [1.06-1.80]). Low ficolin-3 levels (<10.7 mu g/mL) were more common in patients (39.5 %, 30/76) than controls (20.6 %, 13/63, p = 0.018, OR = 2.51 [1.14-5.31]), and in RHD (44.4 %, 28/63) than RFo (15.4 %, 2/13, p = 0.007, OR = 3.08 [1.43-6.79]). On the other hand, FCN3 polymorphism/haplotypes were not associated with ficolin-3 serum levels or the disease. Low ficolin-3 levels might be associated with RF, being a potential marker of disease progression.
- 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.
- Understanding rheumatic fever(2012) AZEVEDO, Pedro Ming; PEREIRA, Rosa Rodrigues; GUILHERME, LuizaThrough a comprehensive review of the recent findings on rheumatic fever, we intend to propose a new physiopathologic model for this disease. A Medline search was performed for all articles containing the terms rheumatic fever or rheumatic heart disease in title or abstract from 1970 to 2011. Best evidence qualitative technique was used to select the most relevant. The scientific interest on rheumatic fever has notably diminished throughout the twentieth century as evidenced by the comparison of the proportion of articles in which RF was a subject in 1950 (0.26%) and today (0.03%) [Pubmed]. However, RF remains a major medical and social problem in the developing world and in the so-called hotspots, where it still causes around 500.000 deaths each year, not too different from the pre-antibiotic era. The role of genetic factors in RF susceptibility is discussed. Familiar aggregation, similarity of disease patterns between siblings, identical twin, and HLA correlation studies are evidence for a genetic influence on RF susceptibility. The suspect-involved genes fall mainly into those capable of immunologic mediation. Molecular mimicry explains the triggering of RF, but an intense and sustained inflammation is needed to cause sequels. Also, RF patients vary greatly in terms of symptoms. It is likely that a genetic background directing immune response towards a predominantly Th1 or Th2 pattern contributes to these features. The recent findings on rheumatic fever provide important insight on its physiopathology that helps understanding this prototype post-infectious autoimmune disease giving insights on other autoimmune conditions.
- Status of research and development of vaccines for Streptococcus pyogenes(2016) STEER, Andrew C.; CARAPETIS, Jonathan R.; DALE, James B.; FRASER, John D.; GOOD, Michael F.; GUILHERME, Luiza; MORELAND, Nicole J.; MULHOLLAND, E. Kim; SCHODEL, Florian; SMEESTERS, Pierre R.Streptococcus pyogenes is an important global pathogen, causing considerable morbidity and mortality, especially in low and middle income countries where rheumatic heart disease and invasive infections are common. There is a number of promising vaccine candidates, most notably those based on the M protein, the key virulence factor for the bacterium. Vaccines against Streptococcus pyogenes are considered as impeded vaccines because of a number of crucial barriers to development Considerable effort is needed by key players to bring current vaccine candidates through phase III clinical trials and there is a clear need to develop a roadmap for future development of current and new candidates. (C) 2016 World Health Organization; licensee Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.orgilicensesiby/3.0/).