SEARCHCASE_REPORTpediatrics, immunology

case_report·pediatrics, immunology, endocrinology, dermatology, clinical trial·PMC10730634

Ruxolitinib Rescues Multiorgan Clinical Autoimmunity in Patients with APS-1

Journal of Clinical Immunology · 14 authors, 13 centres

AI SUMMARY

FIDELITY 100%

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

This is a case series of three adolescents with autoimmune polyendocrine syndrome type-1 (APS-1) treated with the JAK inhibitor ruxolitinib.

Full summary

991 CHARS

This study describes three adolescent patients with APS-1 who received off-label ruxolitinib for autoimmune manifestations including alopecia areata and steroid-dependent autoimmunity. The treatment duration ranged from 25 to 31 months. The authors report a clinically relevant positive impact on multiple autoimmune conditions, such as alopecia areata, nail dystrophy, candidiasis, autoimmune hepatitis, hypoparathyroidism, and others, but note that adrenal insufficiency did not respond. The safety profile was good, with no infectious adverse events observed, except for transient anemia in one patient. The study notes this is the first report of ruxolitinib use in APS-1, suggesting a broad beneficial effect on endocrine components. However, the authors explicitly state the series is too small for strong conclusions, and a prospective clinical trial is warranted. Implications are that JAK/STAT signaling may play a key role in APS-1 pathogenesis, but fundamental studies are needed.

STUDY TYPE

case_report

SPECIALTY

pediatrics

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10730634

Ruxolitinib Rescues Multiorgan Clinical Autoimmunity in Patients with APS-1

Journal of Clinical Immunology

READ THE FULL PAPER

ABSTRACT

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. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-023-01629-x.

CITATION EXPORT

Romain Lévy, Agathe Escudier, Paul Bastard et al.. Ruxolitinib Rescues Multiorgan Clinical Autoimmunity in Patients with APS-1. Journal of Clinical Immunology. (2023). https://doi.org/10.1007/s10875-023-01629-x

AUTHORS

14 · 13 CENTRES

Romain Lévy, Agathe Escudier, Paul Bastard, Coralie Briand, Laura Polivka, Athanasia Stoupa, Cécile Talbotec, Anya Rothenbuhler, Marina Charbit, Dominique Debray, Christine Bodemer, Jean-Laurent Casanova, Agnès Linglart, Bénédicte Neven

1https://ror.org/02vjkv261grid.7429.80000 0001 2186 6389Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, EU France
2grid.462336.6Paris-Cité University, Imagine Institute, Paris, EU France
3grid.412134.10000 0004 0593 9113Pediatric Hematology, Immunology and Rheumatology Unit, Necker Hospital for Sick Children, AP-HP Paris, EU France
4https://ror.org/0420db125grid.134907.80000 0001 2166 1519St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY USA
5https://ror.org/04pag4b70grid.414153.60000 0000 8897 490XDepartment of Pediatrics, Jean Verdier Hospital, AP-HP, Bondy, EU France
6https://ror.org/05rq3rb55grid.462336.6Department of Dermatology, Reference Center for Genodermatoses (MAGEC), Imagine Institute, Necker Hospital for Sick Children, AP-HP Paris, EU France
7grid.412134.10000 0004 0593 9113Pediatric Endocrinology, Gynecology and Diabetology Department, Necker Hospital for Sick Children, AP-HP Paris, EU France
8grid.412134.10000 0004 0593 9113Department of Pediatric Gastroenterology, Necker Hospital for Sick Children, AP-HP Paris, EU France
9grid.50550.350000 0001 2175 4109Department 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
10grid.412134.10000 0004 0593 9113Department of Pediatric Nephrology, Necker Hospital for Sick Children, AP-HP Paris, EU France
11grid.412134.10000 0004 0593 9113Department of Pediatric Hepatology, Necker Hospital for Sick Children, AP-HP Paris, EU France
12https://ror.org/006w34k90grid.413575.10000 0001 2167 1581Howard Hughes Medical Institute, New York, NY USA
13https://ror.org/03xjwb503grid.460789.40000 0004 4910 6535Paris Saclay University, INSERM U1185, Bicêtre Paris Saclay Hospital, Le Kremlin-Bicêtre, EU France