Homozygous N-terminal missense mutation in TRNT1 leads to progressive B-cell immunodeficiency in adulthood Glynis Frans, MPharm, Leen Moens, PhD, Heidi.

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Presentation transcript:

Homozygous N-terminal missense mutation in TRNT1 leads to progressive B-cell immunodeficiency in adulthood Glynis Frans, MPharm, Leen Moens, PhD, Heidi Schaballie, MD, Greet Wuyts, BSc, Adrian Liston, PhD, Koen Poesen, MPharm, PhD, Ann Janssens, MD, PhD, Gillian I. Rice, PhD, Yanick J. Crow, MD, PhD, Isabelle Meyts, MD, PhD, Xavier Bossuyt, MD, PhD Journal of Allergy and Clinical Immunology Volume 139, Issue 1, Pages 360-363.e6 (January 2017) DOI: 10.1016/j.jaci.2016.06.050 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Molecular and functional characterization. A, Pedigree and Sanger sequencing. B, TRNT1 protein structure (PDB ID: 1OU5). Mutation p.R99W is indicated with SIFD-causing mutations.2,4 C, Serum from the patient, his parents, and 4 healthy adult controls was evaluated for IFN-α and IL-6 levels. D, Interferon signature: increased expression level of ISGs in peripheral blood. ISGs, Interferon-stimulated genes; RQ, relative quantification vs 29 healthy controls. Journal of Allergy and Clinical Immunology 2017 139, 360-363.e6DOI: (10.1016/j.jaci.2016.06.050) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Abnormalities in lymphocyte subsets. A, B-cell immunophenotyping: decrease in CD24++CD38++ and CD24−CD38++ cells in the CD19+CD20+ population. Results shown are representative of n = 2 experiments. B, NK-cell phenotyping: Increase in CD56bright cells in the lymphocyte population. Results shown are representative of n = 3 experiments. C, CD107a expression in CD3−CD56+ cells: unstimulated and stimulated with PHA and K562 target cells. Journal of Allergy and Clinical Immunology 2017 139, 360-363.e6DOI: (10.1016/j.jaci.2016.06.050) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Differential white blood cell count and immunophenotyping results. Shaded areas indicate age-specific reference values. E5 Journal of Allergy and Clinical Immunology 2017 139, 360-363.e6DOI: (10.1016/j.jaci.2016.06.050) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 TRNT1 expression in skin-derived fibroblasts from the patient and 3 adult controls. Band intensity was quantified relative to pan-14-3-3 expression. Journal of Allergy and Clinical Immunology 2017 139, 360-363.e6DOI: (10.1016/j.jaci.2016.06.050) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Peripheral blood smears. A, Prussian blue staining reveals no iron granules in the peripheral blood. B, May-Grunwald Giemsa staining shows several neutrophils with toxic granulation. Journal of Allergy and Clinical Immunology 2017 139, 360-363.e6DOI: (10.1016/j.jaci.2016.06.050) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 CD107a expression in PBMCs from a healthy adult control and the patient. Cells were stimulated with K562 target cells and PHA (2.5 μg/mL) for 23 hours at 37°C. CD56 is plotted against CD107a in CD3−CD56+ cells. Journal of Allergy and Clinical Immunology 2017 139, 360-363.e6DOI: (10.1016/j.jaci.2016.06.050) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions