A novel genomic inversion in Wiskott-Aldrich–associated autoinflammation Immacolata Brigida, PhD, Samantha Scaramuzza, PhD, Dejan Lazarevic, MD, Davide.

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A novel genomic inversion in Wiskott-Aldrich–associated autoinflammation Immacolata Brigida, PhD, Samantha Scaramuzza, PhD, Dejan Lazarevic, MD, Davide Cittaro, PhD, Francesca Ferrua, MD, Lorena Leonardelli, PhD, Maria Alessio, MD, Ornella Forma, RN, Chiara Lanzani, MD, Gianluca Viarengo, MD, Fabio Ciceri, MD, Momcilo Jankovic, MD, Fernando Pesce, MD, Alessandro Aiuti, MD, PhD, Maria Pia Cicalese, MD, PhD Journal of Allergy and Clinical Immunology Volume 138, Issue 2, Pages 619-622.e7 (August 2016) DOI: 10.1016/j.jaci.2016.03.007 Copyright © 2016 The Authors Terms and Conditions

Fig 1 Skin lesions and biochemical markers in a patient with WAS with autoinflammatory manifestations. A, Patient at the time of WAS diagnosis. B, Patient after 3 months of treatment with MTX. C, Patient after 5 months of treatment with anakinra. D, Inflammation pattern during several immunosuppressive and antinflammatory treatments administered. Increase in CRP, WBC, and neutrophils (N) at month 4 and amelioration after treatment with anakinra. CRP, C-Reactive protein; IV, intravenous; IVIG, intravenous immunoglobulin; MTX, methotrexate; WBC, white blood cell. Journal of Allergy and Clinical Immunology 2016 138, 619-622.e7DOI: (10.1016/j.jaci.2016.03.007) Copyright © 2016 The Authors Terms and Conditions

Fig 2 Identification of inversion in the WAS gene. A, Pedigree of the family. Proband is indicated by arrow. B, Graphical representation of predicted effects of inversion in the WAS gene. Primer design in the sites of inversion. C, DNA amplification with primers AF/BF and AR/BR in the family. Aspecific band in sample II.2. D, cDNA amplification with indicated primers. Journal of Allergy and Clinical Immunology 2016 138, 619-622.e7DOI: (10.1016/j.jaci.2016.03.007) Copyright © 2016 The Authors Terms and Conditions

Fig E1 Graphical representation of WGS results. WAS gene and coverage are indicated. Primers R1 and R2 for Illumina sequencing that pair correctly are represented in gray. The red lines in the patient indicate the pairing in the region spanning the inversion and their specific orientation. HC, Healthy control; WGS, whole-genome sequencing. Journal of Allergy and Clinical Immunology 2016 138, 619-622.e7DOI: (10.1016/j.jaci.2016.03.007) Copyright © 2016 The Authors Terms and Conditions

Fig E2 WASp expression. A, Flow cytometry characterization of WASp expression in patient and HC lymphocytes. Percentage of WASp+ cells is reported on histograms. Detection of WASp was performed after permeabilization (Cytofix/Cytoperm kit; BD Biosciences, San Jose, Calif) by a noncommercial rabbit polyclonal antibody (“EFOB,” generated against a WASp peptide), kindly provided by GSK. Gray line: negative control. B, Western blot performed on untransformed T-cell line generated in vitro from patient and his parents. Antibody for detection: polyclonal H250 (BD). C, Restoration of WASp expression in a patient's T-cell line after transduction with LV. GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; HC, healthy control; LV, lentiviral vector; Pt, patient. Journal of Allergy and Clinical Immunology 2016 138, 619-622.e7DOI: (10.1016/j.jaci.2016.03.007) Copyright © 2016 The Authors Terms and Conditions