Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions
- Autores
- Martin Fernandez, Marta; Bravo García Morato, María; Gruber, Conor; Murias Loza, Sara; Malik, Muhammad Nasir Hayat; Alsohime, Fahad; Alakeel, Abdullah; Valdez, Rita; Buta, Sofija; Buda, Guadalupe; Marti, Marcelo Adrian; Larralde, Margarita; Boisson, Bertrand; Feito Rodriguez, Marta; Qiu, Xueer; Chrabieh, Maya; Al Ayed, Mohammed; Al Muhsen, Saleh; Desai, Jigar V.; Ferre, Elise M.N.; Rosenzweig, Sergio D.; Amador-Borrero, Blanca; Bravo-Gallego, Luz Yadira; Olmer, Ruth; Merkert, Sylvia; Bret, Montserrat; Sood, Amika K.; Al-rabiaah, Abdulkarim; Temsah, Mohamad Hani; Halwani, Rabih; Hernandez, Michelle Marilyn; Pessler, Frank; Casanova, Jean Laurent; Bustamante, Jacinta; Lionakis, Michail S.; Bogunovic, Dusan
- Año de publicación
- 2020
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Most monogenic disorders have a primary clinical presentation. Inherited ISG15 deficiency, however, has manifested with two distinct presentations to date: susceptibility to mycobacterial disease and intracranial calcifications from hypomorphic interferon-II (IFN-II) production and excessive IFN-I response, respectively. Accordingly, these patients were managed for their infectious and neurologic complications. Herein, we describe five new patients with six novel ISG15 mutations presenting with skin lesions who were managed for dermatologic disease. Cellularly, we denote striking specificity to the IFN-I response, which was previously assumed to be universal. In peripheral blood, myeloid cells display the most robust IFN-I signatures. In the affected skin, IFN-I signaling is observed in the keratinocytes of the epidermis, endothelia, and the monocytes and macrophages of the dermis. These findings define the specific cells causing circulating and dermatologic inflammation and expand the clinical spectrum of ISG15 deficiency to dermatologic presentations as a third phenotype co-dominant to the infectious and neurologic manifestations.
Fil: Martin Fernandez, Marta. Icahn School Of Medicine At Mount Sinai; Estados Unidos. King Saud University; Arabia Saudita
Fil: Bravo García Morato, María. Instituto de Investigacion del Hospital de la Paz.; España
Fil: Gruber, Conor. Icahn School Of Medicine At Mount Sinai; Estados Unidos. King Saud University; Arabia Saudita
Fil: Murias Loza, Sara. Instituto de Investigacion del Hospital de la Paz.; España
Fil: Malik, Muhammad Nasir Hayat. Twincore; Alemania. University Of Lahore; Países Bajos. Leibniz Universitat Hannover; Alemania. Helmholtz Gemeinschaft; Alemania
Fil: Alsohime, Fahad. King Saud University; Arabia Saudita
Fil: Alakeel, Abdullah. King Saud University; Arabia Saudita
Fil: Valdez, Rita. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; Argentina
Fil: Buta, Sofija. Icahn School Of Medicine At Mount Sinai; Estados Unidos
Fil: Buda, Guadalupe. Bitgenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Biología Celular e Histología; Argentina
Fil: Marti, Marcelo Adrian. Bitgenia; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Biología Celular e Histología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Larralde, Margarita. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Boisson, Bertrand. L'institut Des Maladies Génétiques Imagine; Francia. The Rockefeller University; Estados Unidos. Universite de Paris; Francia
Fil: Feito Rodriguez, Marta. Instituto de Investigacion del Hospital de la Paz.; España
Fil: Qiu, Xueer. Icahn School Of Medicine At Mount Sinai; Estados Unidos
Fil: Chrabieh, Maya. L'institut Des Maladies Génétiques Imagine; Francia
Fil: Al Ayed, Mohammed. Najran University; Arabia Saudita
Fil: Al Muhsen, Saleh. King Saud University; Arabia Saudita
Fil: Desai, Jigar V.. National Institutes of Health; Estados Unidos
Fil: Ferre, Elise M.N.. National Institutes of Health; Estados Unidos
Fil: Rosenzweig, Sergio D.. National Institutes of Health; Estados Unidos
Fil: Amador-Borrero, Blanca. Icahn School Of Medicine At Mount Sinai; Estados Unidos
Fil: Bravo-Gallego, Luz Yadira. Instituto de Investigacion del Hospital de la Paz.; España
Fil: Olmer, Ruth. Hannover Medical School; Alemania. German Center for Lung Research; Alemania
Fil: Merkert, Sylvia. Hannover Medical School; Alemania. German Center for Lung Research; Alemania
Fil: Bret, Montserrat. Instituto de Investigacion del Hospital de la Paz.; España
Fil: Sood, Amika K.. University of North Carolina; Estados Unidos
Fil: Al-rabiaah, Abdulkarim. King Saud University; Arabia Saudita
Fil: Temsah, Mohamad Hani. King Saud University; Arabia Saudita
Fil: Halwani, Rabih. University of Sharjah; Emiratos Arabes Unidos
Fil: Hernandez, Michelle Marilyn. University of North Carolina; Estados Unidos
Fil: Pessler, Frank. Twincore; Alemania. Helmholtz Centre for Infection Research; Alemania
Fil: Casanova, Jean Laurent. The Rockefeller University; Estados Unidos. Necker Hospital for Sick Children; Francia. Howard Hughes Medical Institute; Estados Unidos. Universite de Paris; Francia
Fil: Bustamante, Jacinta. The Rockefeller University; Estados Unidos. Necker Hospital for Sick Children; Francia. Universite de Paris; Francia
Fil: Lionakis, Michail S.. National Institutes of Health; Estados Unidos
Fil: Bogunovic, Dusan. Icahn School Of Medicine At Mount Sinai; Estados Unidos - Materia
-
ENDOTHELIAL CELLS
INBORN ERRORS OF IMMUNITY
ISG15
KERATINOCYTES
MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE
MYELOID CELLS
SKIN INFLAMMATION
TYPE I INTERFERONOPATHY
USP18 - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/182810
Ver los metadatos del registro completo
| id |
CONICETDig_a38e76e67225bf9918601ac01d7b1a7a |
|---|---|
| oai_identifier_str |
oai:ri.conicet.gov.ar:11336/182810 |
| network_acronym_str |
CONICETDig |
| repository_id_str |
3498 |
| network_name_str |
CONICET Digital (CONICET) |
| spelling |
Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin LesionsMartin Fernandez, MartaBravo García Morato, MaríaGruber, ConorMurias Loza, SaraMalik, Muhammad Nasir HayatAlsohime, FahadAlakeel, AbdullahValdez, RitaButa, SofijaBuda, GuadalupeMarti, Marcelo AdrianLarralde, MargaritaBoisson, BertrandFeito Rodriguez, MartaQiu, XueerChrabieh, MayaAl Ayed, MohammedAl Muhsen, SalehDesai, Jigar V.Ferre, Elise M.N.Rosenzweig, Sergio D.Amador-Borrero, BlancaBravo-Gallego, Luz YadiraOlmer, RuthMerkert, SylviaBret, MontserratSood, Amika K.Al-rabiaah, AbdulkarimTemsah, Mohamad HaniHalwani, RabihHernandez, Michelle MarilynPessler, FrankCasanova, Jean LaurentBustamante, JacintaLionakis, Michail S.Bogunovic, DusanENDOTHELIAL CELLSINBORN ERRORS OF IMMUNITYISG15KERATINOCYTESMENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASEMYELOID CELLSSKIN INFLAMMATIONTYPE I INTERFERONOPATHYUSP18https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Most monogenic disorders have a primary clinical presentation. Inherited ISG15 deficiency, however, has manifested with two distinct presentations to date: susceptibility to mycobacterial disease and intracranial calcifications from hypomorphic interferon-II (IFN-II) production and excessive IFN-I response, respectively. Accordingly, these patients were managed for their infectious and neurologic complications. Herein, we describe five new patients with six novel ISG15 mutations presenting with skin lesions who were managed for dermatologic disease. Cellularly, we denote striking specificity to the IFN-I response, which was previously assumed to be universal. In peripheral blood, myeloid cells display the most robust IFN-I signatures. In the affected skin, IFN-I signaling is observed in the keratinocytes of the epidermis, endothelia, and the monocytes and macrophages of the dermis. These findings define the specific cells causing circulating and dermatologic inflammation and expand the clinical spectrum of ISG15 deficiency to dermatologic presentations as a third phenotype co-dominant to the infectious and neurologic manifestations.Fil: Martin Fernandez, Marta. Icahn School Of Medicine At Mount Sinai; Estados Unidos. King Saud University; Arabia SauditaFil: Bravo García Morato, María. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Gruber, Conor. Icahn School Of Medicine At Mount Sinai; Estados Unidos. King Saud University; Arabia SauditaFil: Murias Loza, Sara. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Malik, Muhammad Nasir Hayat. Twincore; Alemania. University Of Lahore; Países Bajos. Leibniz Universitat Hannover; Alemania. Helmholtz Gemeinschaft; AlemaniaFil: Alsohime, Fahad. King Saud University; Arabia SauditaFil: Alakeel, Abdullah. King Saud University; Arabia SauditaFil: Valdez, Rita. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; ArgentinaFil: Buta, Sofija. Icahn School Of Medicine At Mount Sinai; Estados UnidosFil: Buda, Guadalupe. Bitgenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Biología Celular e Histología; ArgentinaFil: Marti, Marcelo Adrian. Bitgenia; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Biología Celular e Histología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Larralde, Margarita. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Boisson, Bertrand. L'institut Des Maladies Génétiques Imagine; Francia. The Rockefeller University; Estados Unidos. Universite de Paris; FranciaFil: Feito Rodriguez, Marta. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Qiu, Xueer. Icahn School Of Medicine At Mount Sinai; Estados UnidosFil: Chrabieh, Maya. L'institut Des Maladies Génétiques Imagine; FranciaFil: Al Ayed, Mohammed. Najran University; Arabia SauditaFil: Al Muhsen, Saleh. King Saud University; Arabia SauditaFil: Desai, Jigar V.. National Institutes of Health; Estados UnidosFil: Ferre, Elise M.N.. National Institutes of Health; Estados UnidosFil: Rosenzweig, Sergio D.. National Institutes of Health; Estados UnidosFil: Amador-Borrero, Blanca. Icahn School Of Medicine At Mount Sinai; Estados UnidosFil: Bravo-Gallego, Luz Yadira. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Olmer, Ruth. Hannover Medical School; Alemania. German Center for Lung Research; AlemaniaFil: Merkert, Sylvia. Hannover Medical School; Alemania. German Center for Lung Research; AlemaniaFil: Bret, Montserrat. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Sood, Amika K.. University of North Carolina; Estados UnidosFil: Al-rabiaah, Abdulkarim. King Saud University; Arabia SauditaFil: Temsah, Mohamad Hani. King Saud University; Arabia SauditaFil: Halwani, Rabih. University of Sharjah; Emiratos Arabes UnidosFil: Hernandez, Michelle Marilyn. University of North Carolina; Estados UnidosFil: Pessler, Frank. Twincore; Alemania. Helmholtz Centre for Infection Research; AlemaniaFil: Casanova, Jean Laurent. The Rockefeller University; Estados Unidos. Necker Hospital for Sick Children; Francia. Howard Hughes Medical Institute; Estados Unidos. Universite de Paris; FranciaFil: Bustamante, Jacinta. The Rockefeller University; Estados Unidos. Necker Hospital for Sick Children; Francia. Universite de Paris; FranciaFil: Lionakis, Michail S.. National Institutes of Health; Estados UnidosFil: Bogunovic, Dusan. Icahn School Of Medicine At Mount Sinai; Estados UnidosElsevier2020-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/182810Martin Fernandez, Marta; Bravo García Morato, María; Gruber, Conor; Murias Loza, Sara; Malik, Muhammad Nasir Hayat; et al.; Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions; Elsevier; Cell Reports; 31; 6; 5-2020; 1-232211-1247CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2211124720305866info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2020.107633info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:20:41Zoai:ri.conicet.gov.ar:11336/182810instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:20:41.738CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions |
| title |
Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions |
| spellingShingle |
Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions Martin Fernandez, Marta ENDOTHELIAL CELLS INBORN ERRORS OF IMMUNITY ISG15 KERATINOCYTES MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE MYELOID CELLS SKIN INFLAMMATION TYPE I INTERFERONOPATHY USP18 |
| title_short |
Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions |
| title_full |
Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions |
| title_fullStr |
Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions |
| title_full_unstemmed |
Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions |
| title_sort |
Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions |
| dc.creator.none.fl_str_mv |
Martin Fernandez, Marta Bravo García Morato, María Gruber, Conor Murias Loza, Sara Malik, Muhammad Nasir Hayat Alsohime, Fahad Alakeel, Abdullah Valdez, Rita Buta, Sofija Buda, Guadalupe Marti, Marcelo Adrian Larralde, Margarita Boisson, Bertrand Feito Rodriguez, Marta Qiu, Xueer Chrabieh, Maya Al Ayed, Mohammed Al Muhsen, Saleh Desai, Jigar V. Ferre, Elise M.N. Rosenzweig, Sergio D. Amador-Borrero, Blanca Bravo-Gallego, Luz Yadira Olmer, Ruth Merkert, Sylvia Bret, Montserrat Sood, Amika K. Al-rabiaah, Abdulkarim Temsah, Mohamad Hani Halwani, Rabih Hernandez, Michelle Marilyn Pessler, Frank Casanova, Jean Laurent Bustamante, Jacinta Lionakis, Michail S. Bogunovic, Dusan |
| author |
Martin Fernandez, Marta |
| author_facet |
Martin Fernandez, Marta Bravo García Morato, María Gruber, Conor Murias Loza, Sara Malik, Muhammad Nasir Hayat Alsohime, Fahad Alakeel, Abdullah Valdez, Rita Buta, Sofija Buda, Guadalupe Marti, Marcelo Adrian Larralde, Margarita Boisson, Bertrand Feito Rodriguez, Marta Qiu, Xueer Chrabieh, Maya Al Ayed, Mohammed Al Muhsen, Saleh Desai, Jigar V. Ferre, Elise M.N. Rosenzweig, Sergio D. Amador-Borrero, Blanca Bravo-Gallego, Luz Yadira Olmer, Ruth Merkert, Sylvia Bret, Montserrat Sood, Amika K. Al-rabiaah, Abdulkarim Temsah, Mohamad Hani Halwani, Rabih Hernandez, Michelle Marilyn Pessler, Frank Casanova, Jean Laurent Bustamante, Jacinta Lionakis, Michail S. Bogunovic, Dusan |
| author_role |
author |
| author2 |
Bravo García Morato, María Gruber, Conor Murias Loza, Sara Malik, Muhammad Nasir Hayat Alsohime, Fahad Alakeel, Abdullah Valdez, Rita Buta, Sofija Buda, Guadalupe Marti, Marcelo Adrian Larralde, Margarita Boisson, Bertrand Feito Rodriguez, Marta Qiu, Xueer Chrabieh, Maya Al Ayed, Mohammed Al Muhsen, Saleh Desai, Jigar V. Ferre, Elise M.N. Rosenzweig, Sergio D. Amador-Borrero, Blanca Bravo-Gallego, Luz Yadira Olmer, Ruth Merkert, Sylvia Bret, Montserrat Sood, Amika K. Al-rabiaah, Abdulkarim Temsah, Mohamad Hani Halwani, Rabih Hernandez, Michelle Marilyn Pessler, Frank Casanova, Jean Laurent Bustamante, Jacinta Lionakis, Michail S. Bogunovic, Dusan |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
ENDOTHELIAL CELLS INBORN ERRORS OF IMMUNITY ISG15 KERATINOCYTES MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE MYELOID CELLS SKIN INFLAMMATION TYPE I INTERFERONOPATHY USP18 |
| topic |
ENDOTHELIAL CELLS INBORN ERRORS OF IMMUNITY ISG15 KERATINOCYTES MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE MYELOID CELLS SKIN INFLAMMATION TYPE I INTERFERONOPATHY USP18 |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
Most monogenic disorders have a primary clinical presentation. Inherited ISG15 deficiency, however, has manifested with two distinct presentations to date: susceptibility to mycobacterial disease and intracranial calcifications from hypomorphic interferon-II (IFN-II) production and excessive IFN-I response, respectively. Accordingly, these patients were managed for their infectious and neurologic complications. Herein, we describe five new patients with six novel ISG15 mutations presenting with skin lesions who were managed for dermatologic disease. Cellularly, we denote striking specificity to the IFN-I response, which was previously assumed to be universal. In peripheral blood, myeloid cells display the most robust IFN-I signatures. In the affected skin, IFN-I signaling is observed in the keratinocytes of the epidermis, endothelia, and the monocytes and macrophages of the dermis. These findings define the specific cells causing circulating and dermatologic inflammation and expand the clinical spectrum of ISG15 deficiency to dermatologic presentations as a third phenotype co-dominant to the infectious and neurologic manifestations. Fil: Martin Fernandez, Marta. Icahn School Of Medicine At Mount Sinai; Estados Unidos. King Saud University; Arabia Saudita Fil: Bravo García Morato, María. Instituto de Investigacion del Hospital de la Paz.; España Fil: Gruber, Conor. Icahn School Of Medicine At Mount Sinai; Estados Unidos. King Saud University; Arabia Saudita Fil: Murias Loza, Sara. Instituto de Investigacion del Hospital de la Paz.; España Fil: Malik, Muhammad Nasir Hayat. Twincore; Alemania. University Of Lahore; Países Bajos. Leibniz Universitat Hannover; Alemania. Helmholtz Gemeinschaft; Alemania Fil: Alsohime, Fahad. King Saud University; Arabia Saudita Fil: Alakeel, Abdullah. King Saud University; Arabia Saudita Fil: Valdez, Rita. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; Argentina Fil: Buta, Sofija. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Buda, Guadalupe. Bitgenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Biología Celular e Histología; Argentina Fil: Marti, Marcelo Adrian. Bitgenia; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Biología Celular e Histología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Larralde, Margarita. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina Fil: Boisson, Bertrand. L'institut Des Maladies Génétiques Imagine; Francia. The Rockefeller University; Estados Unidos. Universite de Paris; Francia Fil: Feito Rodriguez, Marta. Instituto de Investigacion del Hospital de la Paz.; España Fil: Qiu, Xueer. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Chrabieh, Maya. L'institut Des Maladies Génétiques Imagine; Francia Fil: Al Ayed, Mohammed. Najran University; Arabia Saudita Fil: Al Muhsen, Saleh. King Saud University; Arabia Saudita Fil: Desai, Jigar V.. National Institutes of Health; Estados Unidos Fil: Ferre, Elise M.N.. National Institutes of Health; Estados Unidos Fil: Rosenzweig, Sergio D.. National Institutes of Health; Estados Unidos Fil: Amador-Borrero, Blanca. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Bravo-Gallego, Luz Yadira. Instituto de Investigacion del Hospital de la Paz.; España Fil: Olmer, Ruth. Hannover Medical School; Alemania. German Center for Lung Research; Alemania Fil: Merkert, Sylvia. Hannover Medical School; Alemania. German Center for Lung Research; Alemania Fil: Bret, Montserrat. Instituto de Investigacion del Hospital de la Paz.; España Fil: Sood, Amika K.. University of North Carolina; Estados Unidos Fil: Al-rabiaah, Abdulkarim. King Saud University; Arabia Saudita Fil: Temsah, Mohamad Hani. King Saud University; Arabia Saudita Fil: Halwani, Rabih. University of Sharjah; Emiratos Arabes Unidos Fil: Hernandez, Michelle Marilyn. University of North Carolina; Estados Unidos Fil: Pessler, Frank. Twincore; Alemania. Helmholtz Centre for Infection Research; Alemania Fil: Casanova, Jean Laurent. The Rockefeller University; Estados Unidos. Necker Hospital for Sick Children; Francia. Howard Hughes Medical Institute; Estados Unidos. Universite de Paris; Francia Fil: Bustamante, Jacinta. The Rockefeller University; Estados Unidos. Necker Hospital for Sick Children; Francia. Universite de Paris; Francia Fil: Lionakis, Michail S.. National Institutes of Health; Estados Unidos Fil: Bogunovic, Dusan. Icahn School Of Medicine At Mount Sinai; Estados Unidos |
| description |
Most monogenic disorders have a primary clinical presentation. Inherited ISG15 deficiency, however, has manifested with two distinct presentations to date: susceptibility to mycobacterial disease and intracranial calcifications from hypomorphic interferon-II (IFN-II) production and excessive IFN-I response, respectively. Accordingly, these patients were managed for their infectious and neurologic complications. Herein, we describe five new patients with six novel ISG15 mutations presenting with skin lesions who were managed for dermatologic disease. Cellularly, we denote striking specificity to the IFN-I response, which was previously assumed to be universal. In peripheral blood, myeloid cells display the most robust IFN-I signatures. In the affected skin, IFN-I signaling is observed in the keratinocytes of the epidermis, endothelia, and the monocytes and macrophages of the dermis. These findings define the specific cells causing circulating and dermatologic inflammation and expand the clinical spectrum of ISG15 deficiency to dermatologic presentations as a third phenotype co-dominant to the infectious and neurologic manifestations. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020-05 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/182810 Martin Fernandez, Marta; Bravo García Morato, María; Gruber, Conor; Murias Loza, Sara; Malik, Muhammad Nasir Hayat; et al.; Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions; Elsevier; Cell Reports; 31; 6; 5-2020; 1-23 2211-1247 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/182810 |
| identifier_str_mv |
Martin Fernandez, Marta; Bravo García Morato, María; Gruber, Conor; Murias Loza, Sara; Malik, Muhammad Nasir Hayat; et al.; Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions; Elsevier; Cell Reports; 31; 6; 5-2020; 1-23 2211-1247 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2211124720305866 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2020.107633 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
| eu_rights_str_mv |
openAccess |
| rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
| dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
| dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
| reponame_str |
CONICET Digital (CONICET) |
| collection |
CONICET Digital (CONICET) |
| instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
| _version_ |
1844614189996310528 |
| score |
13.070432 |