Dr. Antonio Condino-Neto

@article{pmid39576310,

title = {Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C)},

author = {Evangelos Bellos and Dilys Santillo and Pierre Vantourout and Heather R Jackson and Amedine Duret and Henry Hearn and Yoann Seeleuthner and Estelle Talouarn and Stephanie Hodeib and Harsita Patel and Oliver Powell and Sophya Yeoh and Sobia Mustafa and Dominic Habgood-Coote and Samuel Nichols and Leire Estramiana Elorrieta and Giselle D'Souza and Victoria J Wright and Diego Estrada-Rivadeneyra and Adriana H Tremoulet and Kirsten B Dummer and Stejara A Netea and Antonio Condino-Neto and Yu Lung Lau and Esmeralda Núñez Cuadros and Julie Toubiana and Marisol Holanda Pena and Frédéric Rieux-Laucat and Charles-Edouard Luyt and Filomeen Haerynck and Jean Louis Mège and Samya Chakravorty and Elie Haddad and Marie-Paule Morin and Özge Metin Akcan and Sevgi Keles and Melike Emiroglu and Gulsum Alkan and Sadiye Kübra Tüter Öz and Sefika Elmas Bozdemir and Guillaume Morelle and Alla Volokha and Yasemin Kendir-Demirkol and Betul Sözeri and Taner Coskuner and Aysun Yahsi and Belgin Gulhan and Saliha Kanik-Yuksek and Gulsum Iclal Bayhan and Aslinur Ozkaya-Parlakay and Osman Yesilbas and Nevin Hatipoglu and Tayfun Ozcelik and Alexandre Belot and Emilie Chopin and Vincent Barlogis and Esra Sevketoglu and Emin Menentoglu and Zeynep Gokce Gayretli Aydin and Marketa Bloomfield and Suzan A AlKhater and Cyril Cyrus and Yuriy Stepanovskiy and Anastasiia Bondarenko and Fatma Nur Öz and Meltem Polat and Jiří Fremuth and Jan Lebl and Amyrath Geraldo and Emmanuelle Jouanguy and and and and Michael J Carter and Paul Wellman and Mark Peters and Rebeca Pérez de Diego and Lindsey Ann Edwards and Christopher Chiu and Mahdad Noursadeghi and Alexandre Bolze and Chisato Shimizu and Myrsini Kaforou and Melissa Shea Hamilton and Jethro A Herberg and Erica G Schmitt and Agusti Rodriguez-Palmero and Aurora Pujol and Jihoon Kim and Aurélie Cobat and Laurent Abel and Shen-Ying Zhang and Jean-Laurent Casanova and Taco W Kuijpers and Jane C Burns and Michael Levin and Adrian C Hayday and Vanessa Sancho-Shimizu},

doi = {10.1084/jem.20240699},

issn = {1540-9538},

year  = {2024},

date = {2024-12-01},

urldate = {2024-12-01},

journal = {J Exp Med},

volume = {221},

number = {12},

abstract = {Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.2, 95% CI: 3.5-5.3, P < 10-6). BTNL8 encodes an intestinal epithelial regulator of Vγ4+γδ T cells implicated in regulating gut homeostasis. Enrichment was exclusive to MIS-C, being absent in patients with COVID-19 or bacterial disease. Using an available functional test for BTNL8, rare variants from a larger cohort of MIS-C patients (n = 835) were tested which identified eight variants in 18 patients (2.2%) with impaired engagement of Vγ4+γδ T cells. Most of these variants were in the B30.2 domain of BTNL8 implicated in sensing epithelial cell status. These findings were associated with altered intestinal permeability, suggesting a possible link between disrupted gut homeostasis and MIS-C-associated enteropathy triggered by SARS-CoV-2.},

keywords = {genética},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39365299,

title = {First Brazilian Case Report of Unrelated Patients with Identical ISG15 Mutation},

author = {Sarah Maria da Silva Napoleao and Ranieri Coelho Salgado and Janaira Fernandes Severo Ferreira and Mayra de Barros Dorna and Thais Costa Lima de Moura and Tábata Takahashi França and Lucila Akune Barreiros and Lillian Nunes Gomes and Antonio Condino-Neto},

doi = {10.1007/s10875-024-01811-9},

issn = {1573-2592},

year  = {2024},

date = {2024-10-01},

urldate = {2024-10-01},

journal = {J Clin Immunol},

volume = {45},

number = {1},

pages = {21},

abstract = {BACKGROUND: ISG15 deficiency is a mixed syndrome of Mendelian susceptibility to mycobacterial infections (MSMD), a rare inherited condition characterized primarily by recurrent infections from low-virulence mycobacteria and monogenic type I interferonopathy.nnOBJECTIVE: To characterize the laboratory and molecular features of two patients from different families affected by the same ISG15 variant.nnMETHODS: We began with clinical characterization and investigation, assessed IL-12/IFN-γ production, performed genetic characterization through WES and Sanger sequencing, conducted an in silico molecular analysis of the genetic ISG15 variant's protein impact, and utilized RNAseq for transcriptome analysis to understand pathway impacts on ISG15-deficient subjects from unrelated families.nnRESULTS: A mutation in the ISG15 gene was identified, affecting two patients treated in different hospitals and cities in Brazil (Fortaleza and Sao Paulo), who are also members of unrelated families. Both patients showed low IFN-γ production when stimulated with BCG or BCG + IL-12. ISG15 deficiency presented with two distinct clinical phenotypes: infectious and neurological. It was identified that both patients are homozygous for the variant (c.83 T > A). Furthermore, it was observed that the mutant protein p.L28Q results in an unstable protein with increased flexibility (ΔΔG: -2.400 kcal/mol). Transcriptome analysis revealed 1321 differentially expressed genes, with significant upregulation in interferon pathways, showing higher expression in patients compared to controls.nnCONCLUSION: This study describes the first reported cases in Brazil of two unrelated patients with the same ISG15 mutation c.83 T > A, exhibiting infectious features such as mycobacterial infections and systemic candidiasis, neurological findings, and skin lesions, without adverse reactions to the BCG vaccine.nnCLINICAL IMPLICATIONS: Reporting ISG15 gene mutations in Brazilian patients enhances understanding of genetic susceptibilities, guiding effective diagnostics and treatment. Identifying high-risk individuals aids clinical practices, genetic counseling, and influences public health policies. We have identified the first case in Brazil of the same ISG15 variant c.83 T > A that was identified in two unrelated patients with distinct clinical phenotypes, infectious and neurological.},

keywords = {genética},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38484269,

title = {Autosomal Recessive IL-12p40 Deficiency due to a Mutation in the Gene: Report of a Brazilian Patient with Lymph Node Mycobacterial Infection},

author = {Karina Mescouto de Melo and Fabíola Scancetti Tavares and Thales Silva Antunes and Antonio Condino-Neto and Gesmar Rodrigues Silva Segundo and Antônio Carlos Tanajura de Macedo and Alexandre Paz Ferreira and Cláudia França Cavalcante Valente},

doi = {10.1089/ped.2022.0206},

issn = {2151-3228},

year  = {2024},

date = {2024-03-01},

urldate = {2024-03-01},

journal = {Pediatr Allergy Immunol Pulmonol},

volume = {37},

number = {1},

pages = {33--36},

abstract = { Autosomal recessive interleukin (IL)-12p40 deficiency is a genetic etiology of Mendelian susceptibility to mycobacterial disease (MSMD). It has been described in ∼50 patients, usually with onset at childhood with Bacille Calmette-Guérin (BCG) and  infections.  A male patient born to consanguineous parents was diagnosed with presumed lymph node MSMD at the age of 13 years after ocular symptoms. A positive history of inborn error of immunity was present: BCG reaction, skin abscess, and recurrent oral candidiasis. Abnormal measurements of cytokine levels, IL-12p40 and interferon-gamma (IFN-γ), lead to the diagnosis of MSMD. Genetic analysis showed a mutation in exon 7 of the  gene. Currently, the patient is alive under prophylactic antibiotics.  We report a rare case of IL-12p40 deficiency in a Latin American patient. Medical history was crucial for immune defect suspicion, as confirmed by precision diagnostic medicine tools.},

keywords = {genética},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38287514,

title = {Severe combined immunodeficiency diagnosis and genetic defects},

author = {Carolina Sanchez Aranda and Mariana Pimentel Gouveia-Pereira and Celso Jose Mendanha da Silva and Maria Candida Faria Varanda Rizzo and Edson Ishizuka and Edgar Borges de Oliveira and Antonio Condino-Neto},

doi = {10.1111/imr.13310},

issn = {1600-065X},

year  = {2024},

date = {2024-03-01},

urldate = {2024-03-01},

journal = {Immunol Rev},

volume = {322},

number = {1},

pages = {138--147},

abstract = {Severe combined immunodeficiency (SCID) is a rare and life-threatening genetic disorder that severely impairs the immune system's ability to defend the body against infections. Often referred to as the "bubble boy" disease, SCID gained widespread recognition due to the case of David Vetter, a young boy who lived in a sterile plastic bubble to protect him from germs. SCID is typically present at birth, and it results from genetic mutations that affect the development and function of immune cells, particularly T cells and B cells. These immune cells are essential for identifying and fighting off infections caused by viruses, bacteria, and fungi. In SCID patients, the immune system is virtually non-existent, leaving them highly susceptible to recurrent, severe infections. There are several forms of SCID, with varying degrees of severity, but all share common features. Newborns with SCID often exhibit symptoms such as chronic diarrhea, thrush, skin rashes, and persistent infections that do not respond to standard treatments. Without prompt diagnosis and intervention, SCID can lead to life-threatening complications and a high risk of mortality. There are over 20 possible affected genes. Treatment options for SCID primarily involve immune reconstitution, with the most well-known approach being hematopoietic stem cell transplantation (HSCT). Alternatively, gene therapy is also available for some forms of SCID. Once treated successfully, SCID patients can lead relatively normal lives, but they may still require vigilant infection control measures and lifelong medical follow-up to manage potential complications. In conclusion, severe combined immunodeficiency is a rare but life-threatening genetic disorder that severely compromises the immune system's function, rendering affected individuals highly vulnerable to infections. Early diagnosis and appropriate treatment are fundamental. With this respect, newborn screening is progressively and dramatically improving the prognosis of SCID.},

keywords = {genética, imunidade},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36617817,

title = {Allergy, asthma, and proteomics: opportunities with immediate impact},

author = {Renata Harumi Cruz and Leticia Gomes de Pontes and Antonio Condino-Neto},

doi = {10.15586/aei.v51i1.567},

issn = {1578-1267},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Allergol Immunopathol (Madr)},

volume = {51},

number = {1},

pages = {16--21},

abstract = {Allergy is widely discussed by researchers due to its complex mechanism that leads to disorders and injuries, but the reason behind the allergic status remains unclear. Current treatments are insufficient to improve the patient's quality of life significantly. New technologies in scientific and technological development are emerging. For instance, the union between allergy and peptidomics and bioinformatics tools may help fill the gaps in this field, diagnosis, and treatment. In this review, we look at peptidomics and address some findings, such as target proteins or biomarkers that help better understand mechanisms that lead to inflammation, organ damage, and, consequently, poor quality of life or even death.},

keywords = {alergias, asma, genética},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33417088,

title = {Inherited GATA2 Deficiency Is Dominant by Haploinsufficiency and Displays Incomplete Clinical Penetrance},

author = {Carmen Oleaga-Quintas and Edgar Borges de Oliveira-Júnior and Jérémie Rosain and Franck Rapaport and Caroline Deswarte and Antoine Guérin and Sairaj Munavar Sajjath and Yu Jerry Zhou and Stéphane Marot and Claire Lozano and Lidia Branco and Nuria Fernández-Hidalgo and Dukhee Betty Lew and Anne-Sophie Brunel and Caroline Thomas and Elise Launay and Andrés Augusto Arias and Alexis Cuffel and Vanesa Cunill Monjo and Anna-Lena Neehus and Laura Marques and Manon Roynard and Marcela Moncada-Vélez and Bengü Gerçeker and Roger Colobran and Marie-Gabrielle Vigué and Gabriela Lopez-Herrera and Laura Berron-Ruiz and Nora Hilda Segura Méndez and Patricia O'Farrill Romanillos and Tom Le Voyer and Anne Puel and Christine Bellanné-Chantelot and Kacy A Ramirez and Lazaro Lorenzo-Diaz and Noé Ramirez Alejo and Rebeca Pérez de Diego and Antonio Condino-Neto and Fethi Mellouli and Carlos Rodriguez-Gallego and Torsten Witte and José Franco Restrepo and Mariana Jobim and Stéphanie Boisson-Dupuis and Eric Jeziorski and Claire Fieschi and Guillaume Vogt and Jean Donadieu and Marlène Pasquet and Julia Vasconcelos and Fatma Omur Ardeniz and Mónica Martínez-Gallo and Regis A Campos and Luiz Fernando Jobim and Rubén Martínez-Barricarte and Kang Liu and Aurélie Cobat and Laurent Abel and Jean-Laurent Casanova and Jacinta Bustamante},

doi = {10.1007/s10875-020-00930-3},

issn = {1573-2592},

year  = {2021},

date = {2021-04-01},

urldate = {2021-04-01},

journal = {J Clin Immunol},

volume = {41},

number = {3},

pages = {639--657},

abstract = {PURPOSE: Germline heterozygous mutations of GATA2 underlie a variety of hematological and clinical phenotypes. The genetic, immunological, and clinical features of GATA2-deficient patients with mycobacterial diseases in the familial context remain largely unknown.nnMETHODS: We enrolled 15 GATA2 index cases referred for mycobacterial disease. We describe their genetic and clinical features including their relatives.nnRESULTS: We identified 12 heterozygous GATA2 mutations, two of which had not been reported. Eight of these mutations were loss-of-function, and four were hypomorphic. None was dominant-negative in vitro, and the GATA2 locus was found to be subject to purifying selection, strongly suggesting a mechanism of haploinsufficiency. Three relatives of index cases had mycobacterial disease and were also heterozygous, resulting in 18 patients in total. Mycobacterial infection was the first clinical manifestation in 11 patients, at a mean age of 22.5 years (range: 12 to 42 years). Most patients also suffered from other infections, monocytopenia, or myelodysplasia. Strikingly, the clinical penetrance was incomplete (32.9% by age 40 years), as 16 heterozygous relatives aged between 6 and 78 years, including 4 older than 60 years, were completely asymptomatic.nnCONCLUSION: Clinical penetrance for mycobacterial disease was found to be similar to other GATA2 deficiency-related manifestations. These observations suggest that other mechanisms contribute to the phenotypic expression of GATA2 deficiency. A diagnosis of autosomal dominant GATA2 deficiency should be considered in patients with mycobacterial infections and/or other GATA2 deficiency-related phenotypes at any age in life. Moreover, all direct relatives should be genotyped at the GATA2 locus.},

keywords = {genética},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32533104,

title = {Lentiviral gene therapy rescues p47 chronic granulomatous disease and the ability to fight Salmonella infection in mice},

author = {Andrea Schejtman and Walmir Cutrim Aragão-Filho and Simon Clare and Marta Zinicola and Maren Weisser and Siobhan O Burns and Claire Booth and Hubert B Gaspar and David C Thomas and Antonio Condino-Neto and Adrian J Thrasher and Giorgia Santilli},

doi = {10.1038/s41434-020-0164-6},

issn = {1476-5462},

year  = {2020},

date = {2020-09-01},

urldate = {2020-09-01},

journal = {Gene Ther},

volume = {27},

number = {9},

pages = {459--469},

abstract = {Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency disorder characterised by recurrent and often life-threatening infections and hyperinflammation. It is caused by defects of the phagocytic NADPH oxidase, a multicomponent enzyme system responsible for effective pathogen killing. A phase I/II clinical trial of lentiviral gene therapy is underway for the most common form of CGD, X-linked, caused by mutations in the gp91 subunit of the NADPH oxidase. We propose to use a similar strategy to tackle p47-deficient CGD, caused by mutations in NCF1, which encodes the p47 cytosolic component of the enzymatic complex. We generated a pCCLCHIM-p47 lentiviral vector, containing the chimeric Cathepsin G/FES myeloid promoter and a codon-optimised version of the human NCF1 cDNA. Here we show that transduction with the pCCLCHIM-p47 vector efficiently restores p47 expression and biochemical NADPH oxidase function in p47-deficient human and murine cells. We also tested the ability of our gene therapy approach to control infection by challenging p47-null mice with Salmonella Typhimurium, a leading cause of sepsis in CGD patients, and found that mice reconstituted with lentivirus-transduced hematopoietic stem cells had a reduced bacterial load compared with untreated mice. Overall, our results potentially support the clinical development of a gene therapy approach using the pCCLCHIM-p47 vector.},

keywords = {genética},

pubstate = {published},

tppubtype = {article}

}