Unknown

Dataset Information

0

Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions.


ABSTRACT: 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.

SUBMITTER: Martin-Fernandez M 

PROVIDER: S-EPMC7331931 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions.

Martin-Fernandez Marta M   Bravo García-Morato María M   Gruber Conor C   Murias Loza Sara S   Malik Muhammad Nasir Hayat MNH   Alsohime Fahad F   Alakeel Abdullah A   Valdez Rita R   Buta Sofija S   Buda Guadalupe G   Marti Marcelo A MA   Larralde Margarita M   Boisson Bertrand B   Feito Rodriguez Marta M   Qiu Xueer X   Chrabieh Maya M   Al Ayed Mohammed M   Al Muhsen Saleh S   Desai Jigar V JV   Ferre Elise M N EMN   Rosenzweig Sergio D SD   Amador-Borrero Blanca B   Bravo-Gallego Luz Yadira LY   Olmer Ruth R   Merkert Sylvia S   Bret Montserrat M   Sood Amika K AK   Al-Rabiaah Abdulkarim A   Temsah Mohamad Hani MH   Halwani Rabih R   Hernandez Michelle M   Pessler Frank F   Casanova Jean-Laurent JL   Bustamante Jacinta J   Lionakis Michail S MS   Bogunovic Dusan D  

Cell reports 20200501 6


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  ...[more]

Similar Datasets

| S-EPMC8043375 | biostudies-literature
| S-EPMC3507439 | biostudies-literature
| S-EPMC3873154 | biostudies-literature
2021-03-23 | GSE162760 | GEO
| S-EPMC5793803 | biostudies-literature
| S-EPMC3727650 | biostudies-literature
| S-EPMC7491304 | biostudies-literature
| S-EPMC6746312 | biostudies-literature
| S-EPMC6391094 | biostudies-literature
| S-EPMC4502663 | biostudies-literature