Efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173 -activating mutations in 3 children

• Published in: Journal of allergy and clinical immunology Vol. 138; no. 6; pp. 1752 - 1755
• Main Authors: Frémond, Marie-Louise, MD, Rodero, Mathieu Paul, PhD, Jeremiah, Nadia, PhD, Belot, Alexandre, MD, PhD, Jeziorski, Eric, MD, Duffy, Darragh, PhD, Bessis, Didier, MD, Cros, Guilhem, MD, Rice, Gillian I., PhD, Charbit, Bruno, MSc, Hulin, Anne, PharmD, PhD, Khoudour, Nihel, MD, Caballero, Consuelo Modesto, MD, Bodemer, Christine, MD, PhD, Fabre, Monique, MD, Berteloot, Laureline, MD, Le Bourgeois, Muriel, MD, Reix, Philippe, MD, Walzer, Thierry, PhD, Moshous, Despina, MD, PhD, Blanche, Stéphane, MD, PhD, Fischer, Alain, MD, PhD, Bader-Meunier, Brigitte, MD, Rieux-Laucat, Fréderic, PhD, Crow, Yanick Joseph, MD, PhD, Neven, Bénédicte, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2016; Elsevier Limited; Elsevier
• Subjects: Allergy and Immunology; Bacteriology; Child; Child, Preschool; Disease; Drug dosages; Female; Humans; Immunology; Inflammation; Janus Kinase 1 - antagonists & inhibitors; Janus Kinase 1 - genetics; Janus Kinase 2 - antagonists & inhibitors; Janus Kinase 2 - genetics; Life Sciences; Lymphocytes; Male; Membrane Proteins - genetics; Microbiology and Parasitology; Mortality; Mutation; Mutation - genetics; Patients; Phosphorylation; Protein Kinase Inhibitors - therapeutic use; Pyrazoles - therapeutic use; Virology; Janus Kinase 2; Membrane Proteins; Protein Kinase Inhibitors; Pyrazoles; Humans; Preschool; Female; Male; Mutation; Child; Janus Kinase 1
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2016.07.015

The patients, aged between 5 and 12 years, exhibited the phenotypic variability associated with TMEM173-activating mutations,2-4 with lung disease and systemic inflammation being the major features in patient 1 (P1) and patient 3 (P3), while in patient 2 (P2) skin involvement was most prominent (Fig 1; see Supplemental Text and Table E1 in this article's Online Repository at www.jacionline.org). Modest and incomplete downregulation of ISG was recently described in splenic B cells of mice treated with tofacitinib, a JAK1/3 inhibitor, with differential signaling effects suggesting currently poorly understood facets of IFN regulation.9 In this regard, our kinetic ex vivo experiments provide insights into the rapid dynamic changes in IFN signaling secondary to JAK1 blockade.