Use of ruxolitinib to successfully treat chronic mucocutaneous candidiasis caused by gain-of-function signal transducer and activator of transcription.

Slides:

Advertisements

Similar presentations

Impaired TH17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

Advertisements

Maria B. Sukkar, PhD, Shaoping Xie, PhD, Nadia M

Anju T. Peters, MD, Atsushi Kato, PhD, Ning Zhang, PhD, David B

Disseminated Mycobacterium genavense infection after immunosuppressive therapy shows underlying new composite heterozygous mutations of β1 subunit of.

Plasmacytoid dendritic cell depletion in DOCK8 deficiency: Rescue of severe herpetic infections with IFN-α 2b therapy Sevgi Keles, MD, Haifa H. Jabara,

Forkhead box protein 3 in human nasal polyp regulatory T cells is regulated by the protein suppressor of cytokine signaling 3 Feng Lan, MD, Nan Zhang,

Combined immunodeficiency due to JAK3 mutation in a child presenting with skin granuloma Alessia Scarselli, MD, Silvia Di Cesare, BSc, Gigliola Di Matteo,

Homozygous N-terminal missense mutation in TRNT1 leads to progressive B-cell immunodeficiency in adulthood Glynis Frans, MPharm, Leen Moens, PhD, Heidi.

Forkhead box protein 3 in human nasal polyp regulatory T cells is regulated by the protein suppressor of cytokine signaling 3 Feng Lan, MD, Nan Zhang,

Impaired TH17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

Reduced IFN-γ receptor expression and attenuated IFN-γ response by dendritic cells in patients with atopic dermatitis Eva Gros, MSc, Susanne Petzold,

Anju T. Peters, MD, Atsushi Kato, PhD, Ning Zhang, PhD, David B

Differential cytokine induction by the human skin–associated autoallergen thioredoxin in sensitized patients with atopic dermatitis and healthy control.

IL-10 disrupts the Brd4-docking sites to inhibit LPS-induced CXCL8 and TNF-α expression in monocytes: Implications for chronic obstructive pulmonary disease

T-cell regulation during viral and nonviral asthma exacerbations

Penicillium marneffei infection and impaired IFN-γ immunity in humans with autosomal- dominant gain-of-phosphorylation STAT1 mutations Pamela P.W. Lee,

IFN-γ orchestrates mesenchymal stem cell plasticity through the signal transducer and activator of transcription 1 and 3 and mammalian target of rapamycin.

Chronic mucocutaneous candidiasis associated with an SH2 domain gain-of-function mutation that enhances STAT1 phosphorylation Ali Sobh, MD, Janet Chou,

Reduction of CRKL expression in patients with partial DiGeorge syndrome is associated with impairment of T-cell functions Mauro Giacomelli, PhD, Rajesh.

IL-4 confers resistance to IL-27–mediated suppression on CD4+ T cells by impairing signal transducer and activator of transcription 1 signaling Zhihong.

Inhibition of differentiation, amplification, and function of human TH17 cells by intravenous immunoglobulin Mohan S. Maddur, DVM, Janakiraman Vani,

Is 9 more than 2 also in allergic airway inflammation?

Lung T-cell responses to nontypeable Haemophilus influenzae in patients with chronic obstructive pulmonary disease Paul T. King, MD, PhD, Steven Lim,

Recurrent viral infections associated with a homozygous CORO1A mutation that disrupts oligomerization and cytoskeletal association Christina S. Yee,

Flow cytometric measurement of STAT1 and STAT3 phosphorylation in CD4+ and CD8+ T cells—clinical applications in primary immunodeficiency diagnostics

Dawn C. Newcomb, PhD, Madison G

Aaruni Khanolkar, MBBS, PhD, Dawn A. Kirschmann, PhD, Edward A

Clara cell 16-kd protein downregulates TH2 differentiation of human naive neonatal T cells Sofi Johansson, MSc, Göran Wennergren, MD, PhD, Nils Åberg,

CD4+CD25+ T-regulatory cells are decreased in patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy Kelli R. Ryan, PhD, Catherine.

Lieuwe D. Bos, MSc, PhD, Peter J. Sterk, MD, PhD, Stephen J

Miriam Wittmann, MD, Jana Zeitvogel, Dong Wang, MD, Thomas Werfel, MD

Kathleen R. Bartemes, BA, Gail M. Kephart, BS, Stephanie J

Corticosteroid insensitivity of chemokine expression in airway smooth muscle of patients with severe asthma Po-Jui Chang, MD, Pankaj K. Bhavsar, PhD,

Gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1): Chronic mucocutaneous candidiasis accompanied by enamel defects.

Steroid resistance of airway type 2 innate lymphoid cells from patients with severe asthma: The role of thymic stromal lymphopoietin Sucai Liu, PhD,

Merritt L. Fajt, MD, Stacy L

Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor–dependent innate antiviral immune responses Douglas R. McDonald, MD, PhD,

Peter M. Wolfgram, MD, David B. Allen, MD

T-box 21 transcription factor is responsible for distorted TH2 differentiation in human peripheral CD4+ T cells Osamu Kaminuma, DVM, PhD, Fujiko Kitamura,

Inhibition of human B-cell development into plasmablasts by histone deacetylase inhibitor valproic acid Anne-Kathrin Kienzler, MSc, Marta Rizzi, MD,

Gain-of-function signal transducer and activator of transcription 1 (STAT1) mutation– related primary immunodeficiency is associated with disseminated.

Impaired natural killer cell functions in patients with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations Giovanna.

Zoulfia Allakhverdi, PhD, Michael R. Comeau, BSc, Dirk E

Elucidating the effects of disease-causing mutations on STAT3 function in autosomal- dominant hyper-IgE syndrome Simon J. Pelham, MSc, Helen C. Lenthall,

Exogenous IFN-β has antiviral and anti-inflammatory properties in primary bronchial epithelial cells from asthmatic subjects exposed to rhinovirus Julie.

Baricitinib treatment in a patient with a gain-of-function mutation in signal transducer and activator of transcription 1 (STAT1) Kornvalee Meesilpavikkai,

Staphylococcal exotoxins are strong inducers of IL-22: A potential role in atopic dermatitis Margarete Niebuhr, MD, Helena Scharonow, MS, Merle Gathmann,

In vivo maturation of TH cells in relation to atopy

Josée Lamoureux, PhD, Jana Stankova, PhD, Marek Rola-Pleszczynski, MD

What is an “eosinophilic phenotype” of asthma?

The L412F variant of Toll-like receptor 3 (TLR3) is associated with cutaneous candidiasis, increased susceptibility to cytomegalovirus, and autoimmunity

Increased activation-induced cell death of high IFN-γ–producing TH1 cells as a mechanism of TH2 predominance in atopic diseases Tunc Akkoc, PhD, Pieter.

Direct ex vivo analysis of allergen-specific CD4+ T cells

Extrapulmonary tuberculosis mimicking Mendelian susceptibility to mycobacterial disease in a patient with signal transducer and activator of transcription.

Autophagy: Nobel Prize 2016 and allergy and asthma research

Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment

A novel hypomorphic mutation in STIM1 results in a late-onset immunodeficiency Heidi Schaballie, MD, Rémy Rodriguez, MS, Emmanuel Martin, PhD, Leen Moens,

Matthew J. Loza, PhD, Susan Foster, PhD, Stephen P

Cytokine responses in cord blood predict the severity of later respiratory syncytial virus infection Hanna Juntti, MD, Pamela Österlund, PhD, Jorma Kokkonen,

Signal transducer and activator of transcription 5 tyrosine phosphorylation for the diagnosis and monitoring of patients with severe combined immunodeficiency

Xiu-Min Li, MD, LaVerne Brown, PhD

TH9 immunodeficiency in patients with hyper-IgE syndrome

Pınar Uysal, MD, Esben Eller, MSc, PhD, Charlotte G

CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X- linked–like syndrome, and defective IL-10 expression from CD4 lymphocytes

Janet Chou, MD, Maxim Lutskiy, MD, PhD, Erdyni Tsitsikov, PhD, Luigi D

Anti-inflammatory and corticosteroid-enhancing actions of vitamin D in monocytes of patients with steroid-resistant and those with steroid-sensitive asthma

Common variable immunodeficiency is associated with a functional deficiency of invariant natural killer T cells Yifang Gao, PhD, Sarita Workman, MSc,

Intact IL-12 signaling is necessary for the generation of human natural killer cells with enhanced effector function after restimulation Venkateswara.

Natural history of cow’s milk allergy

Combined immunodeficiency in a patient with c-Rel deficiency

Presentation transcript:

Use of ruxolitinib to successfully treat chronic mucocutaneous candidiasis caused by gain-of-function signal transducer and activator of transcription 1 (STAT1) mutation Eleanor Higgins, MRCPI, Tariq Al Shehri, MSc, Maeve A. McAleer, MRCPI, Niall Conlon, PhD, FRCPath, Conleth Feighery, MD, Desa Lilic, MD, PhD, Alan D. Irvine, MD Journal of Allergy and Clinical Immunology Volume 135, Issue 2, Pages 551-553.e3 (February 2015) DOI: 10.1016/j.jaci.2014.12.1867 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Clinical photographs of the patient at baseline/week 0 (left) and 12 weeks after completion of therapy/week 24 (right). Journal of Allergy and Clinical Immunology 2015 135, 551-553.e3DOI: (10.1016/j.jaci.2014.12.1867) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Western blot of PBMC lysates from healthy control subjects (HC) and our patient with CMC (CMC pt). Cells were left unstimulated or stimulated with IFN-α (1 × 103 IU/mL) for 30 minutes in the presence or absence of ruxolitinib at 1 μmol/L. GAPDH, Glyceraldehgyde-3-phosphate dehydrogenase; pSTAT1, phosphorylated STAT1; pSTAT3, phosphorylated STAT3. Journal of Allergy and Clinical Immunology 2015 135, 551-553.e3DOI: (10.1016/j.jaci.2014.12.1867) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 PBMCs from healthy control subjects (n = 4) and a patient with CMC and a STAT1 GOF mutation were stimulated with live Candida albicans (1:15,000) or PHA (2 mg/mL) or left unstimulated in the presence or absence of 1 μmol/L ruxolitinib for 5 days in RPMI 10% FCS and 2.5 μg/mL amphotericin. IL-17A and IL-22 levels were assessed by using ELISA. Bg, Background. Journal of Allergy and Clinical Immunology 2015 135, 551-553.e3DOI: (10.1016/j.jaci.2014.12.1867) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Flow cytometric trace of phosphorylated STAT1 (pSTAT1) gated on CD3+ lymphocytes. Whole blood from a patient with CMC was stimulated with IFN-γ (1 × 103 IU/mL) for 15 minutes with and without ruxolitinib (Rx) or left unstimulated and then stained with antibodies to CD3–Pacific Blue and pSTAT1–Alexa Fluor 647 antibody by using the BD Biosciences Phosphlow kit. Journal of Allergy and Clinical Immunology 2015 135, 551-553.e3DOI: (10.1016/j.jaci.2014.12.1867) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions