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

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Chronic mucocutaneous candidiasis associated with an SH2 domain gain-of-function mutation that enhances STAT1 phosphorylation Ali Sobh, MD, Janet Chou, MD, Lynda Schneider, MD, Raif S. Geha, MD, Michel J. Massaad, PhD Journal of Allergy and Clinical Immunology Volume 138, Issue 1, Pages 297-299 (July 2016) DOI: 10.1016/j.jaci.2015.12.1320 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 GOF mutation in STAT1. A, Sanger sequencing chromatograms. B, Multiple protein alignment of STAT1 showing the conserved H629. C, Representative histogram of pSTAT1 in EBV-B cells. D, Representative immunoblot of cytoplasmic and nuclear fractions. GAPDH (cytoplasm) and PARP-1 (nucleus) were used as markers. E-F, IL-17A and IL-2 secretion by PBMCs (Fig 1, E) and IP-10 secretion by EBV-B cells (Fig 1, F). Columns and bars represent mean ± SEM of 3 controls and the patient cells in triplicate. Ctrl, Control; GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; IP-10, IFN-γ–induced protein-10; ND, not detected; PARP-1, poly (ADP-Ribose) polymerase 1; Pt, patient. *P < .05 and ***P < .001. Journal of Allergy and Clinical Immunology 2016 138, 297-299DOI: (10.1016/j.jaci.2015.12.1320) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Increased phosphorylation and normal dephosphorylation of H629Y mutant STAT1. A and B, Kinetics of STAT1 phosphorylation in EBV-B cells from the patient and controls without (Fig 2, A) or with the addition of orthovanadate (Fig 2, B). C and D, Decay of pSTAT1 levels (Fig 2, C) and rate of pSTAT1 dephosphorylation (Fig 2, D) in EBV-B cells, following the addition of staurosporine (time 0) for the indicated times. The values in Figure 2, A to D, are from 3 independent experiments using 3 controls and the patient cells in triplicate. Statistics were done by 2-way ANOVA. Ctrl, Control; MFI, mean fluorescence intensity; NS, not significant; Pt, patient. ***P < .001. Journal of Allergy and Clinical Immunology 2016 138, 297-299DOI: (10.1016/j.jaci.2015.12.1320) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions