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Lung Transplantation under a Janus Kinase Inhibitor in Three Patients with SAVI Syndrome

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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.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Service de Pneumologie Pédiatrique, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon, Lyon, France

    Kenza Rhzioual Berrada, Camille Ohlmann & Philippe Reix

  2. Service de Rhumatologie, Néphrologie Et Dermatologie Pédiatrique, CMR RAISE, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon, Lyon, France

    Alexandre Belot

  3. Centre International de Recherche en Infectiologie, Université de Lyon, Institut National de La Santé Et de La Recherche Médicale, U1111, Université Claude Bernard Lyon 1, Lyon, France

    Alexandre Belot

  4. Le Centre National de La Recherche Scientifique, UMR5308, Lyon, France

    Alexandre Belot

  5. Service d’immunologie-Hématologie Et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, Assistance Publique des Hôpitaux de Paris, INSERM, Paris, France

    Bénédicte Neven & Marie-Louise Frémond

  6. Service de Chirurgie Thoracique Et Transplantation Pulmonaire, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France

    François Tronc

  7. School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, Division of Evolution and Genomic Sciences, University of Manchester, Manchester, UK

    Gillian Rice

  8. Service de Pneumologie Pédiatrique, Assistance Publique-Hôpitaux de Paris, Hôpital Armand Trousseau, Paris, France

    Guillaume Thouvenin

  9. Centre de Recherche St Antoine Inserm UMRS.938, UPMC Université Paris Cité 06, Sorbonne Universités, Paris, France

    Guillaume Thouvenin

  10. Service de Pneumologie Pédiatrique, Centre Hospitalier Universitaire Timone Enfants, Assistance Publique-Hôpitaux de Marseille, Université de La Méditerranée, Marseille, France

    Jean-Christophe Dubus, Julie Mazenq & Nathalie Stremler

  11. Institut Imagine, Laboratoire de Neurogénétique Et de Neuroinflammation, Université de Paris, Paris, France

    Marie-Louise Frémond

  12. Service de Chirurgie Thoracique Et Chirurgie Vasculaire, Hôpital Marie Lannelongue, Groupe Hospitalier Paris Saint-Joseph, Plessis-Robinson, France

    Séverine Soummer-Feuillet

  13. UMR-S-99, Inserm, Hôpital Marie Lannelongue, Faculté de Médecine Paris Saclay, Université Paris-Saclay, Plessis-Robinson, France

    Séverine Soummer-Feuillet

  14. Service de Pneumologie, Centre de Référence Des Maladies Pulmonaires Rares, Hôpital Louis Pradel, Hospices Civils de Lyon; UMR754, INRAE, Université Lyon 1, Lyon, France

    Vincent Cottin

  15. CNRS, Laboratoire de Biométrie Et Biologie Evolutive, UMR 5558, Équipe EMET, Université Lyon 1, 69622, Villeurbanne, France

    Philippe Reix

Authors
  1. Kenza Rhzioual Berrada
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  2. Alexandre Belot
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  3. Bénédicte Neven
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  4. Camille Ohlmann
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  5. François Tronc
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  6. Gillian Rice
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  7. Guillaume Thouvenin
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  8. Jean-Christophe Dubus
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  9. Julie Mazenq
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  10. Marie-Louise Frémond
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  12. Séverine Soummer-Feuillet
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  13. Vincent Cottin
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  14. Philippe Reix
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Contributions

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.

Corresponding author

Correspondence to Philippe Reix.

Ethics declarations

Ethics Approval

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.

Consent to Participate

P1 consent was obtained.

Consent for Publication

The parents of P2 and P3 did not oppose the use and publishing of the medical data or images of their children.

Disclosures of Conflict of Interest/Competing Interests

The authors declare having no financial or nonfinancial interests or competing interests that are directly or indirectly related to the work submitted for publication.

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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

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