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

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Presentation on theme: "Use of ruxolitinib to successfully treat chronic mucocutaneous candidiasis caused by gain-of-function signal transducer and activator of transcription."— Presentation transcript:

1 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 e3 (February 2015) DOI: /j.jaci Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 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  , e3DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 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  , e3DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 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  , e3DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 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  , e3DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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