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

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CD4 T cell–restricted IL-2 signaling defect in a patient with a novel IFNGR1 deficiency Aaruni Khanolkar, MBBS, PhD, Dawn A. Kirschmann, PhD, Edward A. Caparelli, BS, Jeffrey D. Wilks, BS, Jillian M. Cerullo, BS, Jenna R.E. Bergerson, MD, MPH, Lawrence J. Jennings, MD, PhD, Ramsay L. Fuleihan, MD Journal of Allergy and Clinical Immunology Volume 141, Issue 1, Pages 435-439.e7 (January 2018) DOI: 10.1016/j.jaci.2017.08.018 Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Assessment of signaling and phenotypic properties of lymphocytes. A, Evaluation of pSTAT1 signal after rhIFN-γ treatment. B, IFN-γR1 surface expression. Ab, Antibody. C, i to iii and v, pSTAT5 signal measured after treatment with rhIL-2 with or without anti–IFN-γ antibody. C, iv, pSTAT1 signal measured after treatment with rhIFN-γ with or without anti–IFN-γ antibody. See the Methods section in this article's Online Repository at www.jacionline.org for additional details. Journal of Allergy and Clinical Immunology 2018 141, 435-439.e7DOI: (10.1016/j.jaci.2017.08.018) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Sanger sequencing of exons 4 and 5 of IFNGR1. DNA was extracted from peripheral blood and sequenced, as described in the Methods section. A deletion in exon 4 leading to a frameshift was observed in both the proband and mother. Conversely, a single nucleotide variant in exon 5 creating a premature termination codon was observed in both the proband and father. Journal of Allergy and Clinical Immunology 2018 141, 435-439.e7DOI: (10.1016/j.jaci.2017.08.018) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 T cell–associated signaling properties and IL-2 receptor expression. A, Evaluation of pSTAT signals after treatment with the indicated cytokines. B, CD25 and CD122 expression patterns. Journal of Allergy and Clinical Immunology 2018 141, 435-439.e7DOI: (10.1016/j.jaci.2017.08.018) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Intracellular cytokine expression profile of T-cell subsets. Expression of the listed cytokine molecules was evaluated in the cytosol of the indicated T-cell subsets in the absense and presence of phorbol 12-myristate 13-acetate/ionomycin (PMA/Ion). Journal of Allergy and Clinical Immunology 2018 141, 435-439.e7DOI: (10.1016/j.jaci.2017.08.018) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Examination of potential cross-interference between IFN-γ and IL-2 signaling pathways. Whole blood sample aliquots from a healthy control subject were pretreated with graded doses of either rhIFN-γ (A) or rhIL-2 (B), followed by conventional Phosflow stimulation with the listed cytokines. The indicated pSTAT molecules were assessed. See the Methods section in this article's Online Repository for additional details. Journal of Allergy and Clinical Immunology 2018 141, 435-439.e7DOI: (10.1016/j.jaci.2017.08.018) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 IFN-γ and IL-2 signaling in an unrelated 17-month-old patient with a confirmed STAT1 defect. A, Evaluation of pSTAT1 signal after treatment with rhIFN-γ. B, Evaluation of pSTAT5 signal after treatment with rhIL-2. Journal of Allergy and Clinical Immunology 2018 141, 435-439.e7DOI: (10.1016/j.jaci.2017.08.018) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions