Gain-of-function variants in STAT3 are known to cause severe, multifaceted autoimmunity. Here we report three individuals with de-novo STAT3 GOF alleles and early-onset, severe interstitial lung disease manifesting during the first 3 years of life. Imaging and histology revealed different forms of interstitial pneumonia alongside fibrotic and cystic tissue destruction. Definitive diagnosis was established by post-mortem whole exome sequencing and functional validation of two new STAT3 variants. Such lung-predominant forms of STAT3 GOF disease expand the phenotypic spectrum of diseases associated with activating STAT3 variants and add to our understanding of this life-threatening inborn error of immunity. This article is protected by copyright. All rights reserved.
- Gothe, F.
- Gehrig, J.
- Rapp, C. K.
- Knoflach, K.
- Reu-Hofer, S.
- Länger, F.
- Schramm, D.
- Ley-Zaporozhan, J.
- Ehl, S.
- Schwerk, N.
- Faletti, L.
- Griese, M.
Keywords
- Stat3
- autoimmunity
- inborn error of immunity
- interstitial lung disease
