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Case report: Pneumocystis jirovecii pneumonia in a severe case of Aicardi–Goutières syndrome with an IFIH1 gain-of-function mutation mimicking combined immunodeficiency

Aicardi–Goutières syndrome (AGS) is a genetically determined early-onset progressive encephalopathy caused by mutations leading to overexpression of type I interferon (IFN) and resulting in various clinical phenotypes. A gain-of-function (GOF) mutation in the IFIH1 gene is associated with robust pro...

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Autores principales: Železnik, Mojca, Soltirovska Šalamon, Aneta, Debeljak, Maruša, Goropevšek, Aleš, Šuštar, Nataša, Ključevšek, Damjana, Ihan, Alojz, Avčin, Tadej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846174/
https://www.ncbi.nlm.nih.gov/pubmed/36685504
http://dx.doi.org/10.3389/fimmu.2022.1033513
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author Železnik, Mojca
Soltirovska Šalamon, Aneta
Debeljak, Maruša
Goropevšek, Aleš
Šuštar, Nataša
Ključevšek, Damjana
Ihan, Alojz
Avčin, Tadej
author_facet Železnik, Mojca
Soltirovska Šalamon, Aneta
Debeljak, Maruša
Goropevšek, Aleš
Šuštar, Nataša
Ključevšek, Damjana
Ihan, Alojz
Avčin, Tadej
author_sort Železnik, Mojca
collection PubMed
description Aicardi–Goutières syndrome (AGS) is a genetically determined early-onset progressive encephalopathy caused by mutations leading to overexpression of type I interferon (IFN) and resulting in various clinical phenotypes. A gain-of-function (GOF) mutation in the IFIH1 gene is associated with robust production of type I IFN and activation of the Janus kinase (JAK) signal transducer and activator of the transcription (STAT) pathway, which can cause AGS type 7. We detail the clinical case of an infant who initially presented with Pneumocystis jirovecii pneumonia (PCP), had recurrent respiratory infections, and was later treated with a JAK inhibitor, baricitinib, because of a genetically confirmed GOF mutation in the IFIH1 gene. This spectrum of IFIH1 GOF mutations with overlapping features of hyperinflammation and severe opportunistic infection, which mimics combined immunodeficiency (CID), has not been described before. In this case, therapy with baricitinib effectively blocked IFN-α activation and reduced STAT1 signaling but had no effect on the progression of the neurological disease.
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spelling pubmed-98461742023-01-19 Case report: Pneumocystis jirovecii pneumonia in a severe case of Aicardi–Goutières syndrome with an IFIH1 gain-of-function mutation mimicking combined immunodeficiency Železnik, Mojca Soltirovska Šalamon, Aneta Debeljak, Maruša Goropevšek, Aleš Šuštar, Nataša Ključevšek, Damjana Ihan, Alojz Avčin, Tadej Front Immunol Immunology Aicardi–Goutières syndrome (AGS) is a genetically determined early-onset progressive encephalopathy caused by mutations leading to overexpression of type I interferon (IFN) and resulting in various clinical phenotypes. A gain-of-function (GOF) mutation in the IFIH1 gene is associated with robust production of type I IFN and activation of the Janus kinase (JAK) signal transducer and activator of the transcription (STAT) pathway, which can cause AGS type 7. We detail the clinical case of an infant who initially presented with Pneumocystis jirovecii pneumonia (PCP), had recurrent respiratory infections, and was later treated with a JAK inhibitor, baricitinib, because of a genetically confirmed GOF mutation in the IFIH1 gene. This spectrum of IFIH1 GOF mutations with overlapping features of hyperinflammation and severe opportunistic infection, which mimics combined immunodeficiency (CID), has not been described before. In this case, therapy with baricitinib effectively blocked IFN-α activation and reduced STAT1 signaling but had no effect on the progression of the neurological disease. Frontiers Media S.A. 2023-01-04 /pmc/articles/PMC9846174/ /pubmed/36685504 http://dx.doi.org/10.3389/fimmu.2022.1033513 Text en Copyright © 2023 Železnik, Soltirovska Šalamon, Debeljak, Goropevšek, Šuštar, Ključevšek, Ihan and Avčin https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Železnik, Mojca
Soltirovska Šalamon, Aneta
Debeljak, Maruša
Goropevšek, Aleš
Šuštar, Nataša
Ključevšek, Damjana
Ihan, Alojz
Avčin, Tadej
Case report: Pneumocystis jirovecii pneumonia in a severe case of Aicardi–Goutières syndrome with an IFIH1 gain-of-function mutation mimicking combined immunodeficiency
title Case report: Pneumocystis jirovecii pneumonia in a severe case of Aicardi–Goutières syndrome with an IFIH1 gain-of-function mutation mimicking combined immunodeficiency
title_full Case report: Pneumocystis jirovecii pneumonia in a severe case of Aicardi–Goutières syndrome with an IFIH1 gain-of-function mutation mimicking combined immunodeficiency
title_fullStr Case report: Pneumocystis jirovecii pneumonia in a severe case of Aicardi–Goutières syndrome with an IFIH1 gain-of-function mutation mimicking combined immunodeficiency
title_full_unstemmed Case report: Pneumocystis jirovecii pneumonia in a severe case of Aicardi–Goutières syndrome with an IFIH1 gain-of-function mutation mimicking combined immunodeficiency
title_short Case report: Pneumocystis jirovecii pneumonia in a severe case of Aicardi–Goutières syndrome with an IFIH1 gain-of-function mutation mimicking combined immunodeficiency
title_sort case report: pneumocystis jirovecii pneumonia in a severe case of aicardi–goutières syndrome with an ifih1 gain-of-function mutation mimicking combined immunodeficiency
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846174/
https://www.ncbi.nlm.nih.gov/pubmed/36685504
http://dx.doi.org/10.3389/fimmu.2022.1033513
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