Ruxolitinib Rescues Multiorgan Clinical Autoimmunity in Patients with APS-1.

AIRE APS-1 Jak inhibitor Ruxolitinib

Journal

Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137

Informations de publication

Date de publication:
19 Dec 2023
Historique:
received: 03 11 2023
accepted: 21 11 2023
medline: 19 12 2023
pubmed: 19 12 2023
entrez: 19 12 2023
Statut: epublish

Résumé

Autoimmune polyendocrine syndrome type-1 (APS-1) is caused by mono- or biallelic loss-of-function variants of the autoimmune regulator gene AIRE underlying early-onset multiorgan autoimmunity and the production of neutralizing autoantibodies against cytokines, accounting for mucosal candidiasis and viral diseases. Medical intervention is essential to prevent or attenuate autoimmune manifestations. Ruxolitinib is a JAK inhibitor approved for use in several autoimmune conditions. It is also used off-label to treat autoimmune manifestations of a growing range of inborn errors of immunity. We treated three APS-1 patients with ruxolitinib and followed them for at least 30 months. Tolerance was excellent, with no medical or biological adverse events. All three patients had remarkably positive responses to ruxolitinib for alopecia, nail dystrophy, keratitis, mucosal candidiasis, steroid-dependent autoimmune hepatitis, exocrine pancreatic insufficiency, renal potassium wasting, hypoparathyroidism, and diabetes insipidus. JAK inhibitors were therefore considered an effective treatment in three patients with APS-1. Our observations suggest that JAK/STAT pathways are involved in the pathogenesis of APS-1 autoimmune manifestations. They also suggest that JAK inhibitors should be tested in a broader range of APS-1 patients.

Identifiants

DOI: 10.1007/s10875-023-01629-x PMID: 38112858
pubmed: 38112858
doi: 10.1007/s10875-023-01629-x
pii: 10.1007/s10875-023-01629-x
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

5

Informations de copyright

© 2023. The Author(s).

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Auteurs

Romain Lévy (R)

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, EU, France. romain.levy@inserm.fr.
Paris-Cité University, Imagine Institute, Paris, EU, France. romain.levy@inserm.fr.
Pediatric Hematology, Immunology and Rheumatology Unit, Necker Hospital for Sick Children, AP-HP, Paris, EU, France. romain.levy@inserm.fr.
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. romain.levy@inserm.fr.
ORCID: 0000-0002-6393-0198

Agathe Escudier (A)

Paris-Cité University, Imagine Institute, Paris, EU, France.
Pediatric Hematology, Immunology and Rheumatology Unit, Necker Hospital for Sick Children, AP-HP, Paris, EU, France.

Paul Bastard (P)

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, EU, France.
Paris-Cité University, Imagine Institute, Paris, EU, France.
Pediatric Hematology, Immunology and Rheumatology Unit, Necker Hospital for Sick Children, AP-HP, Paris, EU, France.
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.

Coralie Briand (C)

Department of Pediatrics, Jean Verdier Hospital, AP-HP, Bondy, EU, France.

Laura Polivka (L)

Paris-Cité University, Imagine Institute, Paris, EU, France.
Department of Dermatology, Reference Center for Genodermatoses (MAGEC), Imagine Institute, Necker Hospital for Sick Children, AP-HP, Paris, EU, France.

Athanasia Stoupa (A)

Pediatric Endocrinology, Gynecology and Diabetology Department, Necker Hospital for Sick Children, AP-HP, Paris, EU, France.

Cécile Talbotec (C)

Department of Pediatric Gastroenterology, Necker Hospital for Sick Children, AP-HP, Paris, EU, France.

Anya Rothenbuhler (A)

Department of Endocrinology and Diabetes for Children; Reference Center for Rare Diseases of Calcium and Phosphate Metabolism, Filière OSCAR, ERN BOND, Endo-ERN, Bicêtre Paris Saclay Hospital, AP-HP, Le Kremlin-Bicêtre, EU, France.

Marina Charbit (M)

Department of Pediatric Nephrology, Necker Hospital for Sick Children, AP-HP, Paris, EU, France.

Dominique Debray (D)

Department of Pediatric Hepatology, Necker Hospital for Sick Children, AP-HP, Paris, EU, France.

Christine Bodemer (C)

Paris-Cité University, Imagine Institute, Paris, EU, France.
Department of Dermatology, Reference Center for Genodermatoses (MAGEC), Imagine Institute, Necker Hospital for Sick Children, AP-HP, Paris, EU, France.

Jean-Laurent Casanova (JL)

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, EU, France.
Paris-Cité University, Imagine Institute, Paris, EU, France.
Pediatric Hematology, Immunology and Rheumatology Unit, Necker Hospital for Sick Children, AP-HP, Paris, EU, France.
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
Howard Hughes Medical Institute, New York, NY, USA.

Agnès Linglart (A)

Department of Endocrinology and Diabetes for Children; Reference Center for Rare Diseases of Calcium and Phosphate Metabolism, Filière OSCAR, ERN BOND, Endo-ERN, Bicêtre Paris Saclay Hospital, AP-HP, Le Kremlin-Bicêtre, EU, France.
Paris Saclay University, INSERM U1185, Bicêtre Paris Saclay Hospital, Le Kremlin-Bicêtre, EU, France.

Bénédicte Neven (B)

Paris-Cité University, Imagine Institute, Paris, EU, France.
Pediatric Hematology, Immunology and Rheumatology Unit, Necker Hospital for Sick Children, AP-HP, Paris, EU, France.

Classifications MeSH