Dr. Antonio Condino-Neto

@article{pmid37119982b,

title = {Improving Access to Therapy for Patients With Inborn Errors of Immunity: A Call to Action},

author = {Morna J Dorsey and Antonio Condino-Neto},

doi = {10.1016/j.jaip.2023.04.019},

issn = {2213-2201},

year  = {2023},

date = {2023-06-01},

journal = {J Allergy Clin Immunol Pract},

volume = {11},

number = {6},

pages = {1698--1702},

abstract = {Breakthroughs in sequencing technology, targeted immunotherapy, and immune reconstituting treatment have increased the pool of patients with inborn errors of immunity, requiring expertise from clinical immunologists. A growing category of immunodeficiency, presenting as primary immune regulatory disorder and secondary immunodeficiency due to targeted immune therapy for cancer and autoimmunity, has added to the growing burden of patients needing access to immune-supportive therapy. The confluence of a growing population of patients needing a clinical immunologist, complex payer structures, and inadequate health care representation will exacerbate current problems with access to therapy. Patients, health care providers, researchers, public and private payers, and industry must come together to find solutions to improve access to therapy. In this article, we reviewed the major topics regarding access to therapy for patients with immunodeficiency.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37119982,

title = {Improving Access to Therapy for Patients With Inborn Errors of Immunity: A Call to Action},

author = {Morna J Dorsey and Antonio Condino-Neto},

doi = {10.1016/j.jaip.2023.04.019},

issn = {2213-2201},

year  = {2023},

date = {2023-06-01},

urldate = {2023-06-01},

journal = {J Allergy Clin Immunol Pract},

volume = {11},

number = {6},

pages = {1698--1702},

abstract = {Breakthroughs in sequencing technology, targeted immunotherapy, and immune reconstituting treatment have increased the pool of patients with inborn errors of immunity, requiring expertise from clinical immunologists. A growing category of immunodeficiency, presenting as primary immune regulatory disorder and secondary immunodeficiency due to targeted immune therapy for cancer and autoimmunity, has added to the growing burden of patients needing access to immune-supportive therapy. The confluence of a growing population of patients needing a clinical immunologist, complex payer structures, and inadequate health care representation will exacerbate current problems with access to therapy. Patients, health care providers, researchers, public and private payers, and industry must come together to find solutions to improve access to therapy. In this article, we reviewed the major topics regarding access to therapy for patients with immunodeficiency.},

keywords = {Erros Inatos da Imunidade},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37198208b,

title = {A novel insight on SARS-CoV-2 S-derived fragments in the control of the host immunity},

author = {Thais Sibioni Berti Bastos and André Guilherme Portela de Paula and Rebeca Bosso Dos Santos Luz and Anali M B Garnique and Marco A A Belo and Silas Fernandes Eto and Dayanne Carla Fernandes and Fausto Klabund Ferraris and Leticia Gomes de Pontes and Tábata Takahashi França and Leonardo José Gil Barcellos and Flavio P Veras and Pamela Bermejo and Giovanna Guidelli and Carla Maneira and Fellipe da Silveira Bezerra de Mello and Gleidson Teixeira and Gonçalo Amarante Guimarães Pereira and Bianca H Ventura Fernandes and Paulo R S Sanches and Helyson Lucas Bezerra Braz and Roberta Jeane Bezerra Jorge and Guilherme Malafaia and Eduardo M Cilli and Danilo da Silva Olivier and Marcos Serrou do Amaral and Renata J Medeiros and Antonio Condino-Neto and Luciani R Carvalho and Glaucia M Machado-Santelli and Ives Charlie-Silva and Jorge Galindo-Villegas and Tárcio Teodoro Braga},

doi = {10.1038/s41598-023-29588-8},

issn = {2045-2322},

year  = {2023},

date = {2023-05-01},

journal = {Sci Rep},

volume = {13},

number = {1},

pages = {8060},

abstract = {Despite all efforts to combat the pandemic of COVID-19, we are still living with high numbers of infected persons, an overburdened health care system, and the lack of an effective and definitive treatment. Understanding the pathophysiology of the disease is crucial for the development of new technologies and therapies for the best clinical management of patients. Since the manipulation of the whole virus requires a structure with an adequate level of biosafety, the development of alternative technologies, such as the synthesis of peptides from viral proteins, is a possible solution to circumvent this problem. In addition, the use and validation of animal models is of extreme importance to screen new drugs and to compress the organism's response to the disease. Peptides derived from recombinant S protein from SARS-CoV-2 were synthesized and validated by in silico, in vitro and in vivo methodologies. Macrophages and neutrophils were challenged with the peptides and the production of inflammatory mediators and activation profile were evaluated. These peptides were also inoculated into the swim bladder of transgenic zebrafish larvae at 6 days post fertilization (dpf) to mimic the inflammatory process triggered by the virus, which was evaluated by confocal microscopy. In addition, toxicity and oxidative stress assays were also developed. In silico and molecular dynamics assays revealed that the peptides bind to the ACE2 receptor stably and interact with receptors and adhesion molecules, such as MHC and TCR, from humans and zebrafish. Macrophages stimulated with one of the peptides showed increased production of NO, TNF-α and CXCL2. Inoculation of the peptides in zebrafish larvae triggered an inflammatory process marked by macrophage recruitment and increased mortality, as well as histopathological changes, similarly to what is observed in individuals with COVID-19. The use of peptides is a valuable alternative for the study of host immune response in the context of COVID-19. The use of zebrafish as an animal model also proved to be appropriate and effective in evaluating the inflammatory process, comparable to humans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37198208,

title = {A novel insight on SARS-CoV-2 S-derived fragments in the control of the host immunity},

author = {Thais Sibioni Berti Bastos and André Guilherme Portela de Paula and Rebeca Bosso Dos Santos Luz and Anali M B Garnique and Marco A A Belo and Silas Fernandes Eto and Dayanne Carla Fernandes and Fausto Klabund Ferraris and Leticia Gomes de Pontes and Tábata Takahashi França and Leonardo José Gil Barcellos and Flavio P Veras and Pamela Bermejo and Giovanna Guidelli and Carla Maneira and Fellipe da Silveira Bezerra de Mello and Gleidson Teixeira and Gonçalo Amarante Guimarães Pereira and Bianca H Ventura Fernandes and Paulo R S Sanches and Helyson Lucas Bezerra Braz and Roberta Jeane Bezerra Jorge and Guilherme Malafaia and Eduardo M Cilli and Danilo da Silva Olivier and Marcos Serrou do Amaral and Renata J Medeiros and Antonio Condino-Neto and Luciani R Carvalho and Glaucia M Machado-Santelli and Ives Charlie-Silva and Jorge Galindo-Villegas and Tárcio Teodoro Braga},

doi = {10.1038/s41598-023-29588-8},

issn = {2045-2322},

year  = {2023},

date = {2023-05-01},

urldate = {2023-05-01},

journal = {Sci Rep},

volume = {13},

number = {1},

pages = {8060},

abstract = {Despite all efforts to combat the pandemic of COVID-19, we are still living with high numbers of infected persons, an overburdened health care system, and the lack of an effective and definitive treatment. Understanding the pathophysiology of the disease is crucial for the development of new technologies and therapies for the best clinical management of patients. Since the manipulation of the whole virus requires a structure with an adequate level of biosafety, the development of alternative technologies, such as the synthesis of peptides from viral proteins, is a possible solution to circumvent this problem. In addition, the use and validation of animal models is of extreme importance to screen new drugs and to compress the organism's response to the disease. Peptides derived from recombinant S protein from SARS-CoV-2 were synthesized and validated by in silico, in vitro and in vivo methodologies. Macrophages and neutrophils were challenged with the peptides and the production of inflammatory mediators and activation profile were evaluated. These peptides were also inoculated into the swim bladder of transgenic zebrafish larvae at 6 days post fertilization (dpf) to mimic the inflammatory process triggered by the virus, which was evaluated by confocal microscopy. In addition, toxicity and oxidative stress assays were also developed. In silico and molecular dynamics assays revealed that the peptides bind to the ACE2 receptor stably and interact with receptors and adhesion molecules, such as MHC and TCR, from humans and zebrafish. Macrophages stimulated with one of the peptides showed increased production of NO, TNF-α and CXCL2. Inoculation of the peptides in zebrafish larvae triggered an inflammatory process marked by macrophage recruitment and increased mortality, as well as histopathological changes, similarly to what is observed in individuals with COVID-19. The use of peptides is a valuable alternative for the study of host immune response in the context of COVID-19. The use of zebrafish as an animal model also proved to be appropriate and effective in evaluating the inflammatory process, comparable to humans.},

keywords = {COVID-19},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37020259b,

title = {Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19},

author = {Daniela Matuozzo and Estelle Talouarn and Astrid Marchal and Peng Zhang and Jeremy Manry and Yoann Seeleuthner and Yu Zhang and Alexandre Bolze and Matthieu Chaldebas and Baptiste Milisavljevic and Adrian Gervais and Paul Bastard and Takaki Asano and Lucy Bizien and Federica Barzaghi and Hassan Abolhassani and Ahmad Abou Tayoun and Alessandro Aiuti and Ilad Alavi Darazam and Luis M Allende and Rebeca Alonso-Arias and Andrés Augusto Arias and Gokhan Aytekin and Peter Bergman and Simone Bondesan and Yenan T Bryceson and Ingrid G Bustos and Oscar Cabrera-Marante and Sheila Carcel and Paola Carrera and Giorgio Casari and Khalil Chaïbi and Roger Colobran and Antonio Condino-Neto and Laura E Covill and Ottavia M Delmonte and Loubna El Zein and Carlos Flores and Peter K Gregersen and Marta Gut and Filomeen Haerynck and Rabih Halwani and Selda Hancerli and Lennart Hammarström and Nevin Hatipoğlu and Adem Karbuz and Sevgi Keles and Christèle Kyheng and Rafael Leon-Lopez and Jose Luis Franco and Davood Mansouri and Javier Martinez-Picado and Ozge Metin Akcan and Isabelle Migeotte and Pierre-Emmanuel Morange and Guillaume Morelle and Andrea Martin-Nalda and Giuseppe Novelli and Antonio Novelli and Tayfun Ozcelik and Figen Palabiyik and Qiang Pan-Hammarström and Rebeca Pérez de Diego and Laura Planas-Serra and Daniel E Pleguezuelo and Carolina Prando and Aurora Pujol and Luis Felipe Reyes and Jacques G Rivière and Carlos Rodriguez-Gallego and Julian Rojas and Patrizia Rovere-Querini and Agatha Schlüter and Mohammad Shahrooei and Ali Sobh and Pere Soler-Palacin and Yacine Tandjaoui-Lambiotte and Imran Tipu and Cristina Tresoldi and Jesus Troya and Diederik van de Beek and Mayana Zatz and Pawel Zawadzki and Saleh Zaid Al-Muhsen and Mohammed Faraj Alosaimi and Fahad M Alsohime and Hagit Baris-Feldman and Manish J Butte and Stefan N Constantinescu and Megan A Cooper and Clifton L Dalgard and Jacques Fellay and James R Heath and Yu-Lung Lau and Richard P Lifton and Tom Maniatis and Trine H Mogensen and Horst von Bernuth and Alban Lermine and Michel Vidaud and Anne Boland and Jean-François Deleuze and Robert Nussbaum and Amanda Kahn-Kirby and France Mentre and Sarah Tubiana and Guy Gorochov and Florence Tubach and Pierre Hausfater and  and  and  and  and  and  and  and  and  and Isabelle Meyts and Shen-Ying Zhang and Anne Puel and Luigi D Notarangelo and Stephanie Boisson-Dupuis and Helen C Su and Bertrand Boisson and Emmanuelle Jouanguy and Jean-Laurent Casanova and Qian Zhang and Laurent Abel and Aurélie Cobat},

doi = {10.1186/s13073-023-01173-8},

issn = {1756-994X},

year  = {2023},

date = {2023-04-01},

journal = {Genome Med},

volume = {15},

number = {1},

pages = {22},

abstract = {BACKGROUND: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.nnMETHODS: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.nnRESULTS: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P = 1.1 × 10) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3-8.2], P = 2.1 × 10). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1-2635.4], P = 3.4 × 10), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3-8.4], P = 7.7 × 10). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10).nnCONCLUSIONS: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37020259,

title = {Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19},

author = {Daniela Matuozzo and Estelle Talouarn and Astrid Marchal and Peng Zhang and Jeremy Manry and Yoann Seeleuthner and Yu Zhang and Alexandre Bolze and Matthieu Chaldebas and Baptiste Milisavljevic and Adrian Gervais and Paul Bastard and Takaki Asano and Lucy Bizien and Federica Barzaghi and Hassan Abolhassani and Ahmad Abou Tayoun and Alessandro Aiuti and Ilad Alavi Darazam and Luis M Allende and Rebeca Alonso-Arias and Andrés Augusto Arias and Gokhan Aytekin and Peter Bergman and Simone Bondesan and Yenan T Bryceson and Ingrid G Bustos and Oscar Cabrera-Marante and Sheila Carcel and Paola Carrera and Giorgio Casari and Khalil Chaïbi and Roger Colobran and Antonio Condino-Neto and Laura E Covill and Ottavia M Delmonte and Loubna El Zein and Carlos Flores and Peter K Gregersen and Marta Gut and Filomeen Haerynck and Rabih Halwani and Selda Hancerli and Lennart Hammarström and Nevin Hatipoğlu and Adem Karbuz and Sevgi Keles and Christèle Kyheng and Rafael Leon-Lopez and Jose Luis Franco and Davood Mansouri and Javier Martinez-Picado and Ozge Metin Akcan and Isabelle Migeotte and Pierre-Emmanuel Morange and Guillaume Morelle and Andrea Martin-Nalda and Giuseppe Novelli and Antonio Novelli and Tayfun Ozcelik and Figen Palabiyik and Qiang Pan-Hammarström and Rebeca Pérez de Diego and Laura Planas-Serra and Daniel E Pleguezuelo and Carolina Prando and Aurora Pujol and Luis Felipe Reyes and Jacques G Rivière and Carlos Rodriguez-Gallego and Julian Rojas and Patrizia Rovere-Querini and Agatha Schlüter and Mohammad Shahrooei and Ali Sobh and Pere Soler-Palacin and Yacine Tandjaoui-Lambiotte and Imran Tipu and Cristina Tresoldi and Jesus Troya and Diederik van de Beek and Mayana Zatz and Pawel Zawadzki and Saleh Zaid Al-Muhsen and Mohammed Faraj Alosaimi and Fahad M Alsohime and Hagit Baris-Feldman and Manish J Butte and Stefan N Constantinescu and Megan A Cooper and Clifton L Dalgard and Jacques Fellay and James R Heath and Yu-Lung Lau and Richard P Lifton and Tom Maniatis and Trine H Mogensen and Horst von Bernuth and Alban Lermine and Michel Vidaud and Anne Boland and Jean-François Deleuze and Robert Nussbaum and Amanda Kahn-Kirby and France Mentre and Sarah Tubiana and Guy Gorochov and Florence Tubach and Pierre Hausfater and and and and and and and and and and Isabelle Meyts and Shen-Ying Zhang and Anne Puel and Luigi D Notarangelo and Stephanie Boisson-Dupuis and Helen C Su and Bertrand Boisson and Emmanuelle Jouanguy and Jean-Laurent Casanova and Qian Zhang and Laurent Abel and Aurélie Cobat},

doi = {10.1186/s13073-023-01173-8},

issn = {1756-994X},

year  = {2023},

date = {2023-04-01},

urldate = {2023-04-01},

journal = {Genome Med},

volume = {15},

number = {1},

pages = {22},

abstract = {BACKGROUND: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.nnMETHODS: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.nnRESULTS: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P = 1.1 × 10) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3-8.2], P = 2.1 × 10). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1-2635.4], P = 3.4 × 10), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3-8.4], P = 7.7 × 10). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10).nnCONCLUSIONS: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.},

keywords = {COVID-19},

pubstate = {published},

tppubtype = {article}

}