Jakinibs for the treatment of immune dysregulation in patients with gain-of-function signal transducer and activator of transcription 1 (STAT1) or STAT3 mutations

Lisa R Forbes; Tiphanie P Vogel; Megan A Cooper; Johana Castro-Wagner; Edith Schussler; Katja G Weinacht; Ashley S Plant; Helen C Su; Eric J Allenspach; Mary Slatter; Mario Abinun; Desa Lilic; Charlotte Cunningham-Rundles; Olive Eckstein; Peter Olbrich; R Paul Guillerman; Niraj C Patel; Yesim Y Demirdag; Christa Zerbe; Alexandra F Freeman; Steven M Holland; Paul Szabolcs; Andrew Gennery; Troy R Torgerson; Joshua D Milner; Jennifer W Leiding

doi:10.1016/j.jaci.2018.07.020

Jakinibs for the treatment of immune dysregulation in patients with gain-of-function signal transducer and activator of transcription 1 (STAT1) or STAT3 mutations

J Allergy Clin Immunol. 2018 Nov;142(5):1665-1669. doi: 10.1016/j.jaci.2018.07.020. Epub 2018 Aug 6.

Authors

Lisa R Forbes¹, Tiphanie P Vogel², Megan A Cooper³, Johana Castro-Wagner⁴, Edith Schussler⁵, Katja G Weinacht⁶, Ashley S Plant⁷, Helen C Su⁸, Eric J Allenspach⁹, Mary Slatter¹⁰, Mario Abinun¹⁰, Desa Lilic¹⁰, Charlotte Cunningham-Rundles⁵, Olive Eckstein¹¹, Peter Olbrich¹², R Paul Guillerman¹³, Niraj C Patel¹⁴, Yesim Y Demirdag¹⁵, Christa Zerbe⁸, Alexandra F Freeman⁸, Steven M Holland⁸, Paul Szabolcs¹⁶, Andrew Gennery¹⁰, Troy R Torgerson⁹, Joshua D Milner¹⁷, Jennifer W Leiding¹⁸

Affiliations

¹ Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Baylor College of Medicine, Houston, Tex; Center for Human Immunobiology, Texas Children's Hospital, Houston, Tex. Electronic address: lisa.forbes@bcm.edu.
² Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Baylor College of Medicine, Houston, Tex; Center for Human Immunobiology, Texas Children's Hospital, Houston, Tex.
³ Department of Pediatrics, Division of Rheumatology, Washington University, St Louis, Mo.
⁴ Division of Allergy and Immunology, Department of Pediatrics, University of South Florida, St Petersburg, Fla.
⁵ Division of Allergy and Immunology and Department of Medicine and Pediatrics, The Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
⁶ Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford School of Medicine, Stanford, Calif.
⁷ Department of Pediatric Oncology, Children's Hospital of Orange County, Orange, Calif.
⁸ Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
⁹ Division of Rheumatology, Department of Pediatrics, University of Washington and Seattle Children's Hospital, Seattle, Wash.
¹⁰ Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation and Primary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle upon Tyne University, United Kingdom.
¹¹ Department of Hematology and Oncology, Texas Children's Cancer Center, Houston, Tex.
¹² Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md; Department of Pediatric Infectious Diseases and Immunopathologies, Institute of Biomedicine Seville (IBiS), University Hospital Virgen del Rocio, Seville, Spain.
¹³ Department of Pediatric Radiology, Texas Children's Hospital and Department of Radiology, Baylor College of Medicine, Houston, Tex.
¹⁴ Department of Pediatrics, Section of Infectious Disease and Immunology, Levine Children's Hospital, Atrium Health, Charlotte, NC.
¹⁵ Department of Pediatrics, Division of Pediatric Allergy and Immunology, College of Physcians and Surgeons of Columbia Univeristy, New York-Presbyterian Morgan Stanley Children's Hospital, New York, NY.
¹⁶ Division of Blood and Marrow Transplantation and Cellular Therapies, University of Pittsburgh, Pittsburgh, Pa.
¹⁷ Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
¹⁸ Division of Allergy and Immunology, Department of Pediatrics, University of South Florida, St Petersburg, Fla; Cancer and Blood Disorders Institute, Johns Hopkins-All Children's Hospital, St Petersburg, Fla. Electronic address: jleiding@health.usf.edu.

Abstract

Treatment of the autoimmune and immune-dysregulatory features of patients with STAT1 GOF or STAT3 GOF disease remains challenging. Jakinibs have been used to treat the severe immune-dysregulation in patients with either STAT1 GOF or STAT3 GOF mutations.

Publication types

Letter
Multicenter Study
Research Support, N.I.H., Intramural

MeSH terms

Adolescent
Adult
Child
Female
Gain of Function Mutation
Humans
Immunologic Deficiency Syndromes / drug therapy
Immunologic Deficiency Syndromes / genetics*
Janus Kinases / antagonists & inhibitors*
Male
Nitriles
Piperidines / therapeutic use
Protein Kinase Inhibitors / therapeutic use
Pyrazoles / therapeutic use
Pyrimidines / therapeutic use
Pyrroles / therapeutic use
STAT1 Transcription Factor / genetics*
STAT3 Transcription Factor / genetics*
Treatment Outcome

Substances

Nitriles
Piperidines
Protein Kinase Inhibitors
Pyrazoles
Pyrimidines
Pyrroles
STAT1 Transcription Factor
STAT1 protein, human
STAT3 Transcription Factor
STAT3 protein, human
ruxolitinib
tofacitinib
Janus Kinases

Abstract

Publication types

MeSH terms

Substances

Grants and funding