Immunologic reconstitution following hematopoietic stem cell transplantation despite lymph node paucity in NF-κB–inducing kinase deficiency Khaoula Ben.

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Presentation transcript:

Immunologic reconstitution following hematopoietic stem cell transplantation despite lymph node paucity in NF-κB–inducing kinase deficiency Khaoula Ben Farhat, PhD, Mohammed F. Alosaimi, MD, Hiba Shendi, MBBS, Suleiman Al-Hammadi, MBBS, Jennifer Jones, BA, Klaus Schwarz, MD, Ansgar Schulz, MD, Laila S. Alawdah, MBBS, Sandra Burchett, MD, MSc, Sultan Albuhairi, MD, Jennifer Whangbo, MD, PhD, Neha Kwatra, MBBS, Hanan E. Shamseldin, MSc, Fowzan S. Alkuraya, MD, Janet Chou, MD, Raif S. Geha, MD Journal of Allergy and Clinical Immunology Volume 143, Issue 3, Pages 1240-1243.e4 (March 2019) DOI: 10.1016/j.jaci.2018.11.003 Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 The NIK Cys306Valfs*2 mutation and its impact on signaling. A, Family pedigree. B, Linear map of NIK. The mutation in our patients is indicated in red, and in the 2 reported kindreds in blue. C, MAP3K14 mRNA expression in fibroblasts from P1 and a healthy control (HC). Data are representative of 3 independent experiments. D, NIK Protein expression in 293T cells transfected with WT NIKmyc or mutated (mut) NIKmyc. E, p100 processing and phosphorylation in unstimulated (unstim) and α-LTβR–stimulated fibroblasts from P1 and HC. Similar data were obtained in 2 independent experiments. F and G, VCAM1 and CCL20 mRNA expression in unstimulated and anti–LTβR-stimulated (Fig 1, F) and unstimulated and TNF-α–stimulated (Fig 1, G) fibroblasts from P1 and HC. Data are representative of 3 independent experiments. Columns and bars represent the mean ± SEM. CCL20, Chemokine (C-C motif) ligand 20; EV, empty vector; Pt, patient; WT, wild-type. *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology 2019 143, 1240-1243.e4DOI: (10.1016/j.jaci.2018.11.003) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 TLR responses in patient P1. TNF-α, IL1β, and IL-6 production in healthy control (HC) and P1 PBMCs after stimulation with PAM3CSK4 (TLR1/2), CLO97 (TLR7/8), and zymosan (TLR2/6) done by a commercial laboratory. Journal of Allergy and Clinical Immunology 2019 143, 1240-1243.e4DOI: (10.1016/j.jaci.2018.11.003) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Lymphoscintigraphy of patient P1 and control. Anterior sweep (A), transmission (B), and planar (C) images from a lymphoscintigram of the bilateral lower extremities after intradermal injection of Technetium-99m sulfur colloid in the feet demonstrate no inguinal nodal transit up to 6 hours of imaging in P1. Two popliteal LNs (black arrows) were visualized throughout the study period. For comparison, a normal lymphoscintigram (D and E) in a 3-year-old male, with visualization of inguinal/pelvic LNs and left popliteal nodes (red arrows) within 45 minutes of injection. The visualization of popliteal nodes in lower extremity lymphoscintigraphy is variable, but was noted unilaterally in both the index and the comparison patient. Early systemic (liver/genitourinary) activity on both these examinations is in keeping with an incidental small amount of venous injection of the radiotracer. Transmission scans (images B and E) using Cobalt-57 flood source are used for anatomic localization. Journal of Allergy and Clinical Immunology 2019 143, 1240-1243.e4DOI: (10.1016/j.jaci.2018.11.003) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Sanger sequencing of the mutation. Results of sanger sequencing of the region surrounding the location of the mutation in MAP3K14 (c.916delT) in a control, P1, P2, P3, and P4. Journal of Allergy and Clinical Immunology 2019 143, 1240-1243.e4DOI: (10.1016/j.jaci.2018.11.003) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions