JORGE ELIAS KALIL FILHO
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
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
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Recessive NLRC4-Autoinflammatory Disease Reveals an Ulcerative Colitis Locus(2022) STEINER, Annemarie; REYGAERTS, Thomas; PONTILLO, Alessandra; CECCHERINI, Isabella; MOECKING, Jonas; MOGHADDAS, Fiona; DAVIDSON, Sophia; CAROLI, Francesco; GROSSI, Alice; CASTRO, Fabio Fernandes Morato; KALIL, Jorge; GOHR, Florian N.; I, Florian Schmidt; BARTOK, Eva; ZILLINGER, Thomas; HARTMANN, Gunther; GEYER, Matthias; GATTORNO, Marco; MENDONCA, Leonardo Oliveira; MASTERS, Seth L.Purpose NLRC4-associated autoinflammatory disease (NLRC4-AID) is an autosomal dominant condition presenting with a range of clinical manifestations which can include macrophage activation syndrome (MAS) and severe enterocolitis. We now report the first homozygous mutation in NLRC4 (c.478G > A, p.A160T) causing autoinflammatory disease with immune dysregulation and find that heterozygous carriers in the general population are at increased risk of developing ulcerative colitis. Methods Circulating immune cells and inflammatory markers were profiled and historical clinical data interrogated. DNA was extracted and sequenced using standard procedures. Inflammasome activation assays for ASC speck formation, pyroptosis, and IL-1 beta/IL-18 secretion confirmed pathogenicity of the mutation in vitro. Genome-wide association of NLRC4 (A160T) with ulcerative colitis was examined using data from the IBD exomes portal. Results A 60-year-old Brazilian female patient was evaluated for recurrent episodes of systemic inflammation from six months of age. Episodes were characterized by recurrent low-grade fever, chills, oral ulceration, uveitis, arthralgia, and abdominal pain, followed by diarrhea with mucus and variable skin rash. High doses of corticosteroids were somewhat effective in controlling disease and anti-IL-1 beta therapy partially controlled symptoms. While on treatment, serum IL-1 beta and IL-18 levels remained elevated. Genetic investigations identified a homozygous mutation in NLRC4 (A160T), inherited in a recessive fashion. Increased ASC speck formation and IL-1 beta/IL-18 secretion confirmed pathogenicity when NLRC4 (A160T) was analyzed in human cell lines. This allele is significantly enriched in patients with ulcerative colitis: OR 2.546 (95% 1.778-3.644), P = 0.01305. Conclusion NLRC4 (A160T) can either cause recessively inherited autoinflammation and immune dysregulation, or function as a heterozygous risk factor for the development of ulcerative colitis.
- Novel allergens from ancient foods: Man e 5 from manioc (Manihot esculenta Crantz) cross reacts with Hev b 5 from latex(2013) SANTOS, Keity Souza; GADERMAIER, Gabriele; VEJVAR, Eva; ARCURI, Helen Andrade; GALVAO, Clovis Eduardo; YANG, Ariana Campos; RESENDE, Virginia Maria Ferreira; MARTINS, Carlo de Oliveira; HIMLY, Martin; MARI, Adriano; LISO, Marina; POMPONI, Debora; BREITENEDER, Heimo; WAGNER, Stefan; KALIL, Jorge; FERREIRA, Fatima; CASTRO, Fabio Fernandes MoratoScope Manioc (Manihot esculenta) is a tuber mainly consumed in the Southern Hemisphere and used worldwide by food and chemistry industry. We aimed to recombinantly produce and characterize the first manioc allergen and evaluate its IgE reactivity in sera of Brazilian and Italian patients. Methods and results The molecule, termed Man e5, was expressed in E. coli, characterized by amino acid analysis, mass spectrometry, circular dichroism, HPLC, and dynamic light scattering. A tertiary structural model of the protein was produced using bioinformatics and susceptibility to pepsin digestion was analyzed in vitro. Based on its high content of charged residues, heat stability, flexibility and lack of secondary structure elements, the allergen was determined a member of the intrinsically disordered protein family. Brazilian patients were selected based on manioc allergy and Italians based on latex allergy and sensitization to Hev b 5.71% of Brazilians and 40% of Italians were in vitro IgE positive to Man e5. Cross-inhibition assays suggest a possible involvement of this allergen in the latex-fruit syndrome. Conclusion Man e5, the first purified allergen from manioc demonstrates IgE cross-reactivity with Hev b 5. Data suggest Hev b 5 might act as primary sensitizer and could therefore lead to allergic manifestations upon manioc consumption without prior exposition.
conferenceObject In vitro NLRP3 inflammasome activation assay assists diagnosis of genetically negative CAPS patients and guides anti-IL1 therapy(2020) MENDONCA, L. O.; TOLEDO-BARROS, M. A. M.; FRANCO, P. A.; GIAVINA-BIANCHI JUNIOR, P. F.; KALIL, J. E.; CASTRO, F. F. Morato; CAROLI, F.; GROSSI, A.; CECCHERINI, I; ROBAZZI, T.; PILEGGI, G. S.; RIVITTI, M. C.; SANCHES JUNIOR, J. A.; GRUMACH, A. S.; GATTORNO, M.; PONTILLO, A.conferenceObject Clinical, genetic and therapeutical findings of two Brazilian patients with cutaneous mastocytosis associated with systemic autoinflammation(2020) MENDONCA, L. O.; PEREIRA, G. D. F.; FRANCO, P. A.; TOLEDO-BARROS, M. A. M.; AGONDI, R. C.; MORATO-CASTRO, F. F.; CAROLI, F.; GROSSI, A.; CECCHERINI, I; PONTILLO, A.; KALIL, J. E.; GATTORNO, M.; GIAVINA-BIANCHI JUNIOR, P. F.conferenceObject A Case Report of a Novel Compound Heterozygous Mutation in a Brazilian Patient with Deficiency of IL1RA (DIRA)(2017) MENDONCA, L. O.; GROSSI, A.; CORDOVA, P. Torres; AMORIM, L. C.; KALIL, J.; CASTRO, F. M.; PONTILLO, A.; CECCHERINI, I.; GATTORNO, M.; BARROS, M. T. Toledo- A case report of a novel compound heterozygous mutation in a Brazilian patient with deficiency of Interleukin-1 receptor antagonist (DIRA)(2020) MENDONCA, Leonardo Oliveira; GROSSI, Alice; CAROLI, Francesco; OLIVEIRA, Robson Aguiar de; KALIL, Jorge; CASTRO, Fabio Fernandes Morato; PONTILLO, Alessandra; CECCHERINI, Isabella; BARROS, Myrthes Anna Maragna Toledo; GATTORNO, MarcoBackground Deficiency of the natural antagonist of interleukin-1 was first described in 2009 and so far 20 patients has been reported. In Brazil just two cases have been reported both carrying the same homozygous 15 bp deletion. Blocking interleukin-1 has changed rate survival for DIRA patients. The use of anakinra and rilonacept has been reported safe and efficient, whereas the selective blockade of interleukin-1 beta, using the monoclonal antibody canakinumab has been reported in a single case only. Case presentation Here we report a case of a 7 years old Brazilian boy that presented with recurrent episodes of systemic inflammation with severe disabling osteomyelitis with mild pustular skin rash. A Next Generation Sequencing gene panel allowed to detect two pathogenic mutations in the IL1RN gene, described in compound heterozygosity. Corticosteroids was effective in controlling inflammation and anti-IL1 beta blocker triggered disease flare. Complete clinical control could be achieved using IL-1 receptor antagonist. Conclusions DIRA is a severe, life threatening autoinflammatory condition with low numbers of patients described all over the world. The mutation p.Asp72_Ile76del in IL1RN is presented in all Brazilian DIRA patients already described and p.Q45* (rs1019766125) is a new mutation affecting the IL1RN gene. Following the pathogenesis of DIRA, blocking both subunits of interleukin one as well as antagonizing the receptor using anakinra or rilonacept seems to be effective. There is just one report using canakinumab for the treatment of DIRA and this is the first report of disease flare using this drug.