Abstract
Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is a very rare autoinflammatory disease related to STING1 mutation. SAVI is mainly characterized by fever attacks and skin and respiratory manifestations such as interstitial lung disease or alveolar hemorrhage. Respiratory involvement occurs in 80% of cases and might progress to severe lung fibrosis and require lung transplantation (LT). Three patients with SAVI who underwent LT have been reported to date. Two of the three patients died months or years after LT due to multiple organ failure or sepsis. However, the diagnosis of SAVI was made after LT, thus preventing the use of targeted therapy, such as the Janus kinase 1 and 2 inhibitor (JAK1/2i) ruxolitinib, which might be beneficial for the respiratory status of these patients. We aimed to report our experience in managing three patients who were followed in three large lung transplantation centers in France and who benefited from ruxolitinib before undergoing LT. We describe posttransplant complications that occurred as well as outcomes.
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Abbreviations
- BLT:
-
Bilateral lung transplant
- BKV:
-
BK virus
- IFN:
-
Interferon
- IFN-I:
-
Type I interferon
- JAK1/2i:
-
Janus kinase 1 and 2 inhibitor
- JAKi:
-
JAK inhibitor
- LT:
-
Lung transplant
- MMF:
-
Mycophenolate mofetil
- P1:
-
Patient 1
- P2:
-
Patient 2
- P3:
-
Patient 3
- SAVI:
-
STING-associated vasculopathy with onset in infancy
- STING:
-
Stimulator of interferon genes
- TE:
-
Thromboembolic
- yo:
-
Years old
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Acknowledgements
We would like to thank the patients and their families for giving us their agreement to share their cases with the medical community.
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KRB, PR, AB and CO designed the study. KRB contacted the patients and families, collected the medical data and wrote the first draft of the manuscript. NM, GT, and SSF provided additional medical information and context and liaised with the patient’s families. KRB, PR, GT, and NS reviewed and edited the images. BN, MLF, AB, and GR supervised the IFN signature analysis and data interpretation and contributed to the gene analysis. PR supervised the manuscript revision, and all authors contributed to the manuscript preparation and commented on the different versions. All the authors have read and approved the final manuscript.
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With respect to French law on clinical research, this study did not require ethical committee approval, but patients and families need to be notified by letter that they have the ability to oppose data collection and publication.
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The parents of P2 and P3 did not oppose the use and publishing of the medical data or images of their children.
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Berrada, K.R., Belot, A., Neven, B. et al. Lung Transplantation under a Janus Kinase Inhibitor in Three Patients with SAVI Syndrome. J Clin Immunol 43, 2156–2164 (2023). https://doi.org/10.1007/s10875-023-01595-4
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DOI: https://doi.org/10.1007/s10875-023-01595-4