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

• DOI: 10.3389/fimmu.2022.1033513
• Publication Date: 2023-01-04T16:04:37Z
• Authors: Mojca Železnik; Aneta Soltirovska...; Maruša Debeljak; Aleš Goropevšek; Nataša Šuštar; Damjana Ključevšek; Alojz Ihan; Tadej Avčin
• Keywords: Primary Immunodeficiency; STAT1; Pneumocystis pneumonia

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 the IFIH1 gene associated with robust production IFN activation Janus kinase (JAK) signal transducer activator transcription (STAT) pathway, which can cause AGS 7. We detail case an infant who initially presented Pneumocystis jirovecii pneumonia (PCP), had recurrent respiratory infections, was later treated JAK inhibitor, baricitinib, because confirmed GOF gene. This spectrum overlapping features hyperinflammation severe opportunistic infection, mimics combined immunodeficiency (CID), has not been described before. In this case, therapy baricitinib effectively blocked IFN-α reduced STAT1 signaling but no effect on progression neurological disease.