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JAK inhibitors to treat STAT3 gain-of-function: a single-center report and literature review.
Atschekzei, Faranaz; Traidl, Stephan; Carlens, Julia; Schütz, Katharina; von Hardenberg, Sandra; Elsayed, Abdulwahab; Ernst, Diana; Risser, Linus; Thiele, Thea; Graalmann, Theresa; Raab, Juliana; Baumann, Ulrich; Witte, Torsten; Sogkas, Georgios.
Afiliación
  • Atschekzei F; Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.
  • Traidl S; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany.
  • Carlens J; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany.
  • Schütz K; Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
  • von Hardenberg S; Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.
  • Elsayed A; Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.
  • Ernst D; Department of Human Genetics, Hannover Medical School, Hannover, Germany.
  • Risser L; Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.
  • Thiele T; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany.
  • Graalmann T; Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.
  • Raab J; Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.
  • Baumann U; Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.
  • Witte T; Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.
  • Sogkas G; Junior Research Group for Translational Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Front Immunol ; 15: 1400348, 2024.
Article en En | MEDLINE | ID: mdl-39247195
ABSTRACT

Objective:

The signal transducer and activator of transcription 3 (STAT3) gain-of-function (GOF) syndrome (STAT3-GOF) is an inborn error of immunity (IEI) characterized by diverse manifestations of immune dysregulation that necessitate systemic immunomodulatory treatment. The blockade of the interleukin-6 receptor and/or the inhibition of the Janus kinases has been commonly employed to treat diverse STAT3-GOF-associated manifestations. However, evidence on long-term treatment outcome, especially in the case of adult patients, is scarce.

Methods:

Clinical data, including laboratory findings and medical imaging, were collected from all seven patients, diagnosed with STAT3-GOF, who have been treated at the Hannover University School, focusing on those who received a Janus kinase (JAK) inhibitor (JAKi). Previously published cases of STAT3-GOF patients who received a JAKi were evaluated, focusing on reported treatment efficacy with respect to diverse STAT3-GOF-associated manifestations of immune dysregulation and safety.

Results:

Five out of seven patients diagnosed with STAT3-GOF were treated with a JAKi, each for a different indication. Including these patients, outcomes of JAKi treatment have been reported for a total of 41 patients. Treatment with a JAKi led to improvement of diverse autoimmune, inflammatory, or lymphoproliferative manifestations of STAT3-GOF and a therapeutic benefit could be documented for all except two patients. Considering all reported manifestations of immune dysregulation in each patient, complete remission was achieved in 10/41 (24.4%) treated patients.

Conclusions:

JAKi treatment improved diverse manifestations of immune dysregulation in the majority of STAT3-GOF patients, representing a promising therapeutic approach. Long-term follow-up data are needed to evaluate possible risks of prolonged treatment with a JAKi.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Transcripción STAT3 / Inhibidores de las Cinasas Janus / Mutación con Ganancia de Función Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Transcripción STAT3 / Inhibidores de las Cinasas Janus / Mutación con Ganancia de Función Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza