Hematopoietic stem cell transplantation rescues the immunologic phenotype and prevents vasculopathy in patients with adenosine deaminase 2 deficiency

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Hematopoietic stem cell transplantation rescues the immunologic phenotype and prevents vasculopathy in patients with adenosine deaminase 2 deficiency Lien Van Eyck, MD, Michael S. Hershfield, MD, Diana Pombal, MSc, Susan J. Kelly, PhD, Nancy J. Ganson, PhD, Leen Moens, PhD, Glynis Frans, MPharm, Heidi Schaballie, MD, Gert De Hertogh, MD, PhD, James Dooley, MSc, Xavier Bossuyt, MD, PhD, Carine Wouters, MD, PhD, Adrian Liston, PhD, Isabelle Meyts, MD, PhD Journal of Allergy and Clinical Immunology Volume 135, Issue 1, Pages 283-287.e5 (January 2015) DOI: 10.1016/j.jaci.2014.10.010 Copyright © 2014 The Authors Terms and Conditions

Fig 1 Serum IL-6 levels and immunoprofiling in ADA2-deficient patients. A, Major blood leukocyte subsets. B, CD4+ T-lymphocyte subsets. C, TH cell lineages. D, CD8+ T-lymphocyte subsets. E, B-cell subsets. P2's values are shown as filled circles, and values of healthy age-matched control subjects are indicated by open circles. Means and SDs (error bars) shown exclude values for the patient. F, IL-6 levels in sera of P1 and P2. The vertical line indicates the moment of HSCT followed by pineal stroke in P1. The gray shading indicates the periods in which P2 was treated with sirolimus. DC, Dendritic cell; mDC, myeloid dendritic cell; NK, natural killer cell; NKT, natural killer T cell; pDC, plasmacytoid dendritic cell; RTE, recent thymic emigrant; TCM, central memory T cell; TEM, effector memory T cell; TEMRA, CD45RA-expressing effector memory T cell; Tfh, follicular T cell; Th17, IL-17–expressing helper T cell; Treg, regulatory T cell. Journal of Allergy and Clinical Immunology 2015 135, 283-287.e5DOI: (10.1016/j.jaci.2014.10.010) Copyright © 2014 The Authors Terms and Conditions

Fig E1 Vasculopathology and immunopathology in patients with ADA2 deficiency. A, Sagittal T1-weighted MRI of P1 showing pineal gland hemorrhage (arrow). B, Hematoxylin and eosin staining of jejunal ulceration in P2 showing chronic ulcer with predominant eosinophils (arrows), some neutrophils and lymphocytes, and very few plasma cells. Plasma cells stained by means of CD138 staining are indicated by arrows in the inset. Journal of Allergy and Clinical Immunology 2015 135, 283-287.e5DOI: (10.1016/j.jaci.2014.10.010) Copyright © 2014 The Authors Terms and Conditions

Fig E2 Familial inheritance of CECR1 mutation. The region of interest in exon 2 of CECR1 was sequenced by means of Sanger sequencing. A-E, Sequence reads for the father (Fig E2, A), mother (Fig E2, B), healthy sibling (HSCT donor; Fig E2, C), patient 1 after HSCT (chimerism accounts for presence of a minor G peak; Fig E2, D), and patient 2 (Fig E2, E). F, Family tree of the affected pedigree, indicating affected patients and CECR1 genotype. Journal of Allergy and Clinical Immunology 2015 135, 283-287.e5DOI: (10.1016/j.jaci.2014.10.010) Copyright © 2014 The Authors Terms and Conditions