JORGE ELIAS KALIL FILHO

(Fonte: Lattes)
Índice h a partir de 2011
33
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina - Líder

Resultados de Busca

Agora exibindo 1 - 10 de 22
  • article 24 Citação(ões) na Scopus
    Anti-Group A Streptococcal Vaccine Epitope STRUCTURE, STABILITY, AND ITS ABILITY TO INTERACT WITH HLA CLASS II MOLECULES
    (2011) GUILHERME, Luiza; ALBA, Martha P.; FERREIRA, Frederico Moraes; OSHIRO, Sandra Emiko; HIGA, Fabio; PATARROYO, Manuel E.; KALIL, Jorge
    Streptococcus pyogenes infections remain a health problem in several countries due to poststreptococcal sequelae. We developed a vaccine epitope (StreptInCor) composed of 55 amino acids residues of the C-terminal portion of the M protein that encompasses both T and B cell protective epitopes. The nuclear magnetic resonance (NMR) structure of the StreptInCor peptide showed that the structure was composed of two microdomains linked by an 18-residue alpha-helix. A chemical stability study of the StreptInCor folding/unfolding process using far-UV circular dichroism showed that the structure was chemically stable with respect to pH and the concentration of urea. The T cell epitope is located in the first microdomain and encompasses 11 out of the 18 alpha-helix residues, whereas the B cell epitope is in the second microdomain and showed no alpha-helical structure. The prediction of StreptInCor epitope binding to different HLA class II molecules was evaluated based on an analysis of the 55 residues and the theoretical possibilities for the processed peptides to fit into the P1, P4, P6, and P9 pockets in the groove of several HLA class II molecules. We observed 7 potential sites along the amino acid sequence of StreptInCor that were capable of recognizing HLA class II molecules (DRB1*, DRB3*, DRB4*, and DRB5*). StreptInCoroverlapping peptides induced cellular and humoral immune responses of individuals bearing different HLA class II molecules and could be considered as a universal vaccine epitope.
  • article 24 Citação(ões) na Scopus
    Adipose Tissue-Derived Stem Cells from Humans and Mice Differ in Proliferative Capacity and Genome Stability in Long-Term Cultures
    (2011) DANOVIZ, Maria Elena; BASSANEZE, Vinicius; NAKAMUTA, Juliana Sanajotti; SANTOS-JUNIOR, Gabriel Ribeiro dos; SAINT-CLAIR, Danilo; BAJGELMAN, Marcio Chaim; FAE, Kellen Cristhina; KALIL, Jorge; MIYAKAWA, Ayumi Aurea; KRIEGER, Jose Eduardo
    Adipose tissue-derived stem cells (ASCs) are among the more attractive adult stem cell options for potential therapeutic applications. Here, we studied and compared the basic biological characteristics of ASCs isolated from humans (hASCs) and mice (mASCs) and maintained in identical culture conditions, which must be examined prior to considering further potential clinical applications. hASCs and mASCs were compared for immunophenotype, differentiation potential, cell growth characteristics, senescence, nuclear morphology, and DNA content. Although both strains of ASCs displayed a similar immunophenotype, the percentage of CD73(+) cells was markedly lower and CD31(+) was higher in mASC than in hASC cultures. The mean population doubling time was 98.08 +/- 6.15 h for hASCs and 52.58 +/- 3.74 h for mASCs. The frequency of nuclear aberrations was noticeably lower in hASCs than in mASCs regardless of the passage number. Moreover, as the cells went through several in vitro passages, mASCs showed changes in DNA content and cell cycle kinetics (frequency of hypodiploid, G0/G1, G2/M, and hyperdiploid cells), whereas all of these parameters remained constant in hASCs. Collectively, these results suggest that mASCs display higher proliferative capacity and are more unstable than hASCs in long-term cultures. These results underscore the need to consider specificities among model systems that may influence outcomes when designing potential human applications.
  • article 30 Citação(ões) na Scopus
    Myocardial gene and protein expression profiles after autoimmune injury in Chagas' disease cardiomyopathy
    (2011) CUNHA-NETO, Edecio; TEIXEIRA, Priscila C.; FONSECA, Simone G.; BILATE, Angelina M.; KALIL, Jorge
    One third of the 16 million of individuals infected by the protozoan Trypanosoma cruzi in Latin America eventually develop chronic Chagas' disease cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy with shorter survival than non-inflammatory cardiomyopathies. The presence of a T cell-rich mononuclear inflammatory infiltrate and the relative scarcity of parasites in the heart suggested that chronic inflammation secondary to the autoimmune recognition of cardiac proteins could be a major pathogenetic mechanism. Sera from CCC patients crossreactively recognize cardiac myosin and T. cruzi protein B13. T cell clones elicited from peripheral blood with T. cruzi B13 protein or its peptides could crossreactively recognize epitopes from cardiac myosin heavy chain. Likewise, CD4+ T cell clones infiltrating CCC myocardium crossreactively recognize cardiac myosin and T. cruzi protein B13, and intralesional T cell lines produce the inflammatory cytokines IFN-gamma and TNF-alpha. Conversely, IFN-gamma-induced genes and chemokines were found to be upregulated in CCC heart samples, and IFN-gamma is able to induce cardiomyocyte expression of atrial natriuretic factor, a key member of the hypertrophy/heart failure signature. Proteomic analysis of CCC heart tissue showed reduced expression of the energy metabolism enzymes. It can be hypothesized that cytokine-induced modulation of cardiomyocyte gene/protein expression may be a novel disease mechanism in CCC, in addition to direct inflammatory damage.
  • article 47 Citação(ões) na Scopus
    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.
  • article 13 Citação(ões) na Scopus
    HLA-DRB1*04:02, DRB1*08:04 and DRB1*14 alleles associated to pemphigus vulgaris in southeastern Brazilian population
    (2011) WEBER, R.; MONTEIRO, F.; PREUHS-FILHO, G.; RODRIGUES, H.; KALIL, J.; MIZIARA, I. D.
  • article 0 Citação(ões) na Scopus
    CD4+T cells from HIV-1-infected patients recognize wild-type and mutant human immunodeficiency virus-1 protease epitopes
    (2011) MULLER, N. G.; ALENCAR, R.; JAMAL, L.; HAMMER, J.; SIDNEY, J.; SETTE, A.; BRINDEIRO, R. M.; KALIL, J.; CUNHA-NETO, E.; MORAES, S. L.
    P>Human immunodeficiency virus (HIV)-1 protease is a known target of CD8+ T cell responses, but it is the only HIV-1 protein in which no fully characterized HIV-1 protease CD4 epitopes have been identified to date. We investigated the recognition of HIV-1 protease by CD4+ T cells from 75 HIV-1-infected, protease inhibitor (PI)-treated patients, using the 5,6-carboxyfluorescein diacetate succinimidyl ester-based proliferation assay. In order to identify putative promiscuous CD4+ T cell epitopes, we used the TEPITOPE algorithm to scan the sequence of the HXB2 HIV-1 protease. Protease regions 4-23, 45-64 and 73-95 were identified; 32 sequence variants of the mentioned regions, encoding frequent PI-induced mutations and polymorphisms, were also tested. On average, each peptide bound to five of 15 tested common human leucocyte antigen D-related (HLA-DR) molecules. More than 80% of the patients displayed CD4+ as well as CD8+ T cell recognition of at least one of the protease peptides. All 35 peptides were recognized. The response was not associated with particular HLA-DR or -DQ alleles. Our results thus indicate that protease is a frequent target of CD4+ along with CD8+ proliferative T cell responses by the majority of HIV-1-infected patients under PI therapy. The frequent finding of matching CD4+ and CD8+ T cell responses to the same peptides may indicate that CD4+ T cells provide cognate T cell help for the maintenance of long-living protease-specific functional CD8+ T cells.
  • article 42 Citação(ões) na Scopus
    TGFB1 and IL8 gene polymorphisms and susceptibility to visceral leishmaniasis
    (2011) FRADE, Amanda Farage; OLIVEIRA, Lea Campos de; COSTA, Dorcas Lamounier; COSTA, Carlos Henrique Nery; AQUINO, Dorlene; WEYENBERGH, Johan Van; BARRAL-NETTO, Manoel; BARRAL, Aldina; KALIL, Jorge; GOLDBERG, Anna Carla
    Visceral leishmaniasis (VL) or Kala-azar is a serious protozoan infectious disease caused by an obligate intracellular parasite. Cytokines have a major role in determining progression and severity of clinical manifestations in VL. We investigated polymorphisms in the TGFB1 and IL8 genes, which are cytokines known to have a role in onset and severity of the disease. Polymorphisms at TGFB1 -509 C/T and +869 T/C, and IL8 -251 A/T were analyzed by a PCR-RFLP technique, in 198 patients with VL, 98 individuals with asymptomatic infection positive for a delayed-type hypersensitivity test (DTH+) and in 101 individuals with no evidence of infection (DTH-). The presence of the T allele in position -509 of the TGFB1 gene conferred a two-fold risk to develop infection both when including those with clinical symptoms (DTH+ and VL, grouped) or when considering DTH+ only, respectively p = 0.007, OR = 1.9 [1.19-3.02] and p = 0.012, OR = 2.01 [1.17-3.79], when compared with DTH- individuals. In addition, occurrence of hemorrhage was associated with TGFB1 -509 T allele. We suggest that the -509 T allele of the TGFB1 gene, a cytokine with a biologically relevant role in the natural history of the disease, may contribute to overall susceptibility to infection by Leishmania and to severity of the clinical disease.
  • article 2 Citação(ões) na Scopus
    The hammock: a reservoir of allergens
    (2011) REGO, Francisca X. M.; GIAVINA-BIANCHI, Pedro; KALIL, Jorge; ARRUDA, L. Karla; TOLEDO-BARROS, Myrthes
    INTRODUCTION: Asthma affects approximately 10% of the world's population. Sensitization to allergens is an important risk factor, and exposure to allergens is associated with disease severity. \ METHODS: We performed skin tests to evaluate allergen sensitization to mites, cockroaches, cats, dogs, and molds in 73 asthmatic patients. Enzyme Linked Immunosorbent Assay was used to assay the mite and cockroach allergens found in dust from the bedding, hammocks, bedroom floors, living rooms, and kitchens of 29 patients and 14 controls. RESULTS: Fifty patients (68.5%) had positive skin test responses. There were positive responses to D. pteronyssinus (52.0%), B. tropicalis (53.4%), T. putrescentiae (15.0%), E. maynei (12.3%), L. destructor (8.2%), B. germanica (20.5%), P. americana (21.9%), Felis catus (10.9%), C. herbarium (2.7%), A. alternata (4.1%), and P. notatun (1.3%). The exposure to mite and cockroach allergens was similar in the patients and the controls. The Dermatophagoides pteronyssinus Group 1 levels were highest in the beds and hammocks. The Blattella germanica Group 1 levels were highest in the kitchens, living rooms and hammocks. DISCUSSION: The positive skin tests to mites, cockroaches and cats were consistent with previous studies. D pteronyssinus was the most prevalent home dust mite, and hammocks were a source of allergens. To improve asthma prophylaxis, it is important to determine its association with mite allergen exposure in hammocks.
  • article 12 Citação(ões) na Scopus
    Non-Human Leukocyte Antigen Antibodies Reactive with Endothelial Cells Could Be Involved in Early Loss of Renal Allografts
    (2011) RONDA, C.; BORBA, S. C. P.; FERREIRA, S. C. P.; GLOTZ, D.; IANHEZ, L. E.; RODRIGUES, H.; VIGGIANI, C. S.; NAHAS, W.; DAVID-NETO, E.; CASTRO, M. C. R.; DAISA, S. R. David; KALIL, J.; PANAJOTOPOULOS, N.
    Preformed donor-specific human leukocyte antigen (HLA) antibodies have been associated with allograft dysfunction and failure. However, recipients of HLA-identical kidneys can develop acute humoral rejection, implicating putative pathogenic antibodies that are directed against non-HLA antigens. We investigated the presence of endothelial cell reactive antibodies in 11 patients who experienced early loss of their transplanted kidneys owing to humoral rejection and 1 loss from renal venal thrombosis. We examined the potential efficacy of intravenous immunoglobulin to block the binding of these antibodies, as previously suggested for anti-HLA antibodies.
  • article 41 Citação(ões) na Scopus
    A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses
    (2011) ROSA, Daniela Santoro; RIBEIRO, Susan Pereira; ALMEIDA, Rafael Ribeiro; MAIRENA, Eliane Conti; POSTOL, Edilberto; KALIL, Jorge; CUNHA-NETO, Edecio
    T-cell based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. Moreover, polyfunctional and long-lived specific memory T cells have been associated to vaccine-induced protection. CD4(+) T cells are important for the generation and maintenance of functional CD8(+) cytotoxic T cells. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18), capable of eliciting broad CD4(+) T cell responses in multiple HLA class II transgenic mice. Here, we evaluated the breadth and functional profile of HIVBr18-induced immune responses in BALB/c mice. Immunized mice displayed high-magnitude, broad CD4(+)/CD8(+) T cell responses, and 8/18 vaccine-encoded peptides were recognized. In addition, HIVBr18 immunization was able to induce polyfunctional CD4(+) and CD8(+) T cells that proliferate and produce any two cytokines (IFN gamma/TNF alpha, IFN gamma/IL-2 or TNF alpha/IL-2) simultaneously in response to HIV-1 peptides. For CD4(+) T cells exclusively, we also detected cells that proliferate and produce all three tested cytokines simultaneously (IFN gamma/TNF alpha/IL-2). The vaccine also generated long-lived central and effector memory CD4(+) T cells, a desirable feature for T-cell based vaccines. By virtue of inducing broad, polyfunctional and long-lived T cell responses against conserved CD4(+) T cell epitopes, combined administration of this vaccine concept may provide sustained help for CD8(+) T cells and antibody responses-elicited by other HIV immunogens.