STAT1 and STAT3 gain of function: clinically heterogenous immune regulatory disorders.
| Autor: | Olbrich P; Sección de Infectología, Reumatología e Inmunología Pediátrica, UGC de Pediatría, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla/Universidad de Sevilla/Consejo Superior de Investigaciones Científicas, Red de Investigación Translacional en Infectología Pediátrica.; Departamento de Farmacología, Pediatría, y Radiología, Facultad de Medicina, Universidad de Sevilla, Seville, Spain., Freeman AF; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Current opinion in allergy and clinical immunology [Curr Opin Allergy Clin Immunol] 2024 Dec 01; Vol. 24 (6), pp. 440-447. Date of Electronic Publication: 2024 Oct 17. |
| DOI: | 10.1097/ACI.0000000000001039 |
| Abstrakt: | Purpose of Review: The identification of STAT1 gain-of-function (GOF) in 2011 and STAT3 GOF in 2014 has advanced our understanding of the host immunity along the JAK/STAT pathway and allowed targeted treatment approaches. We review the clinical features and pathogenesis of STAT1 and STAT3 GOF and how this has shaped new approaches to therapy. Recent Findings: STAT1 GOF, initially described in patients with chronic mucocutaneous candidiasis (CMC) and autoimmune thyroid disease, is now recognized to cause early-onset multisystem autoimmunity and a range of infections. STAT3 GOF comprises mostly lymphoproliferation and autoimmunity but also with varying severity, including some with life threatening organ dysfunction. Treatment has evolved along with the understanding of the pathogenesis, with patients now receiving JAK inhibition to block upstream of the STAT defect with good response in autoimmunity and CMC in STAT1 GOF. Blockade of IL-6 signaling has also been used in STAT3 GOF. Hematopoietic cell transplantation had initial poor outcomes, but outcomes are now improving with focus on the control of inflammation pretransplant. Summary: Understanding the pathogenesis of STAT1 and STAT3 GOF has allowed great recent advancements in therapy, but many questions remain as to the best approach to therapy for each patient's clinical presentation as well as the durability of these therapies. (Copyright © Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.) |
| Databáze: | MEDLINE |
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