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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

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

Authors: 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 A; 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; Pessler, Frank; Casanova, Jean-Laurent; Bustamante, Jacinta; Lionakis, Michail S; Bogunovic, Dusan

Published In Cell Rep, (2020 05 12)

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.

PubMed ID: 32402279 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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