MAGDA MARIA SALES CARNEIRO SAMPAIO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Pediatria, Faculdade de Medicina - Docente
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina - Líder
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
conferenceObject The Extended Clinical Phenotype of 36 Patients with Chronic Mucocutaneous Candidiasis Due to Gain-of-Function Mutations in STAT1(2014) FREDE, N.; DEPNER, M.; RAABE, J.; DOFFINGER, R.; GKRANIA-KLOTSAS, E.; KUMARARATNE, D.; ATKINSON, T. P.; SCHROEDER, H. W.; NIEHUES, T.; DUECKERS, G.; PUCK, J.; EISENSTEIN, E. M.; STRAY-PEDERSEN, A.; BAUMANN, U.; SCHMIDT, R. E.; FRANCO, J. L.; ORREGO, J. C.; BEN-SHOSHAN, M.; MCCUSKER, C.; JACOB, C. M.; CARNEIRO-SAMPAIO, M.; DEVLIN, L. A.; EDGAR, J. D.; HENDERSON, P.; DYRSO, T.; SENEVIRATNE, S. L.; WANDERS, J.; STAUSS, H.; MEYTS, I.; MOENS, L.; JESENAK, M.; GRIMBACHER, B.- The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1(2016) DEPNER, Mark; FUCHS, Sebastian; RAABE, Jan; FREDE, Natalie; GLOCKER, Cristina; DOFFINGER, Rainer; GKRANIA-KLOTSAS, Effrossyni; KUMARARATNE, Dinakantha; ATKINSON, T. Prescott; SCHROEDER JR., Harry W.; NIEHUES, Tim; DUECKERS, Gregor; STRAY-PEDERSEN, Asbjorg; BAUMANN, Ulrich; SCHMIDT, Reinhold; FRANCO, Jose L.; ORREGO, Julio; BEN-SHOSHAN, Moshe; MCCUSKER, Christine; JACOB, Cristina Miuki Abe; CARNEIRO-SAMPAIO, Magda; DEVLIN, Lisa A.; EDGAR, J. David M.; HENDERSON, Paul; RUSSELL, Richard K.; SKYTTE, Anne-Bine; SENEVIRATNE, Suranjith L.; WANDERS, Jennifer; STAUSS, Hans; MEYTS, Isabelle; MOENS, Leen; JESENAK, Milos; KOBBE, Robin; BORTE, Stephan; BORTE, Michael; WRIGHT, Dowain A.; HAGIN, David; TORGERSON, Troy R.; GRIMBACHER, BodoPurpose Gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) result in unbalanced STAT signaling and cause immune dysregulation and immunodeficiency. The latter is often characterized by the susceptibility to recurrent Candida infections, resulting in the clinical picture of chronic mucocutaneous candidiasis (CMC). This study aims to assess the frequency of GOF STAT1 mutations in a large international cohort of CMC patients. Methods STAT1 was sequenced in genomic DNA from 57 CMC patients and 35 healthy family members. The functional relevance of nine different STAT1 variants was shown by flow cytometric analysis of STAT1 phosphorylation in patients' peripheral blood cells (PBMC) after stimulation with interferon (IFN)-alpha, IFN-gamma or interleukin-27 respectively. Extended clinical data sets were collected and summarized for 26 patients. Results Heterozygous mutations within STAT1 were identified in 35 of 57 CMC patients (61 %). Out of 39 familial cases from 11 families, 26 patients (67 %) from 9 families and out of 18 sporadic cases, 9 patients (50 %) were shown to have heterozygous mutations within STAT1. Thirteen distinct STAT1 mutations are reported in this paper. Eight of these mutations are known to cause CMC (p.M202V, p.A267V, p.R274W, p.R274Q, p.T385M, p.K388E, p.N397D, and p.F404Y). However, five STAT1 variants (p.F172L, p.Y287D, p.P293S, p.T385K and p.S466R) have not been reported before in CMC patients. Conclusion STAT1 mutations are frequently observed in patients suffering from CMC. Thus, sequence analysis of STAT1 in CMC patients is advised. Measurement of IFN- or IL-induced STAT1 phosphorylation in PBMC provides a fast and reliable diagnostic tool and should be carried out in addition to genetic testing.
- Inherited ARPC5 mutations cause an actinopathy impairing cell motility and disrupting cytokine signaling(2023) NUNES-SANTOS, Cristiane J.; KUEHN, HyeSun; BOAST, Brigette; HWANG, SuJin; KUHNS, Douglas B.; STODDARD, Jennifer; NIEMELA, Julie E.; FINK, Danielle L.; PITTALUGA, Stefania; ABU-ASAB, Mones; DAVIES, John S.; BARR, Valarie A.; KAWAI, Tomoki; DELMONTE, Ottavia M.; BOSTICARDO, Marita; GAROFALO, Mary; CARNEIRO-SAMPAIO, Magda; SOMECH, Raz; GHARAGOZLOU, Mohammad; PARVANEH, Nima; SAMELSON, Lawrence E.; FLEISHER, Thomas A.; PUEL, Anne; NOTARANGELO, Luigi D.; BOISSON, Bertrand; CASANOVA, Jean-Laurent; DERFALVI, Beata; ROSENZWEIG, Sergio D.We describe the first cases of germline biallelic null mutations in ARPC5, part of the Arp2/3 actin nucleator complex, in two unrelated patients presenting with recurrent and severe infections, early-onset autoimmunity, inflammation, and dysmorphisms. This defect compromises multiple cell lineages and functions, and when protein expression is reestablished in-vitro, the Arp2/3 complex conformation and functions are rescued. As part of the pathophysiological evaluation, we also show that interleukin (IL)-6 signaling is distinctively impacted in this syndrome. Disruption of IL-6 classical but not trans-signaling highlights their differential roles in the disease and offers perspectives for therapeutic molecular targets. Mutations that impact the function of the Arp2/3 complex are known to cause inborn errors of immunity. Here the authors describe biallelic null mutations in the ARPC5 subunit of Arp2/3 that disrupt actin function and cytokine signaling, causing infections, autoimmunity, inflammation and dysmorphisms.
- Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study(2018) BARZAGHI, Federica; HERNANDEZ, Laura Cristina Amaya; NEVEN, Benedicte; RICCI, Silvia; KUCUK, Zeynep Yesim; BLEESING, Jack J.; NADEMI, Zohreh; SLATTER, Mary Anne; ULLOA, Erlinda Rose; SHCHERBINA, Anna; ROPPELT, Anna; WORTH, Austen; SILVA, Juliana; AIUTI, Alessandro; MURGUIA-FAVELA, Luis; SPECKMANN, Carsten; CARNEIRO-SAMPAIO, Magda; FERNANDES, Juliana Folloni; BARIS, Safa; OZEN, Ahmet; KARAKOC-AYDINER, Elif; KIYKIM, Ayca; SCHULZ, Ansgar; STEINMANN, Sandra; NOTARANGELO, Lucia Dora; GAMBINERI, Eleonora; LIONETTI, Paolo; SHEARER, William Thomas; FORBES, Lisa R.; MARTINEZ, Caridad; MOSHOUS, Despina; BLANCHE, Stephane; FISHER, Alain; RUEMMELE, Frank M.; TISSANDIER, Come; OUACHEE-CHARDIN, Marie; RIEUX-LAUCAT, Frederic; CAVAZZANA, Marina; QASIM, Waseem; LUCARELLI, Barbarella; ALBERT, Michael H.; KOBAYASHI, Ichiro; ALONSO, Laura; HEREDIA, Cristina Diaz De; KANEGANE, Hirokazu; LAWITSCHKA, Anita; SEO, Jong Jin; GONZALEZ-VICENT, Marta; DIAZ, Miguel Angel; GOYAL, Rakesh Kumar; SAUER, Martin G.; YESILIPEK, Akif; KIM, Minsoo; YILMAZ-DEMIRDAG, Yesim; BHATIA, Monica; KHLEVNER, Julie; PADILLA, Erick J. Richmond; MARTINO, Silvana; MONTIN, Davide; NETH, Olaf; MOLINOS-QUINTANA, Agueda; VALVERDE-FERNANDEZ, Justo; BROIDES, Arnon; PINSK, Vered; BALLAUF, Antje; HAERYNCK, Filomeen; BORDON, Victoria; DHOOGE, Catharina; GARCIA-LLORET, Maria Laura; BREDIUS, Robbert G.; KAWAK, Krzysztof; HADDAD, Elie; SEIDEL, Markus Gerhard; DUCKERS, Gregor; PAI, Sung-Yun; DVORAK, Christopher C.; EHL, Stephan; LOCATELLI, Franco; GOLDMAN, Frederick; GENNERY, Andrew Richard; COWAN, Mort J.; RONCAROLO, Maria-Grazia; BACCHETTA, RosaBackground: Immunodysregulation polyendocrinopathy enteropathy x-linked(IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. Objective: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. Methods: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. Results: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n 5 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. Conclusions: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term.disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.
conferenceObject MUTATION SCREENING IN STAT1, CARD9 AND PKC-DELTA IN PATIENTS WITH CHRONIC MUCOCUTANEOUS CANDIDIASIS(2012) DEPNER, M.; VEERDONK, F. van de; WANDERS, J.; STAUSS, H.; RAABE, J.; ATKINSON, T. P.; SCHROEDER JR., H. W.; NIEHUES, T.; DUECKERS, G.; PUCK, J.; STRAY-PEDERSEN, A.; BAUMANN, U.; SCHMIDT, R.; FRANCO, J. L.; ORREGO, J.; BEN-SHOSHAN, M.; MCCUSKER, C.; JACOB, C. M. A.; CARNEIRO-SAMPAIO, M.; DEVLIN, L. A.; EDGAR, J. D.; GKRANIA-KLOTSAS, E.; KUMARARATNE, D.; DOFFINGER, R.; HENDERSON, P.; RUSSELL, R. K.; DYRSO, T.; SENEVIRATNE, S. L.; MATTHIJS, G.; ABINUN, M.; GENNERY, A.; JOHNSON, M.; MEER, J. W. M. van der; NETEA, M. G.; LILIC, D.; GRIMBACHER, B.