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Β2-Microglobulin deficiency causes a complex immunodeficiency of the innate and adaptive immune system  Ömür Ardeniz, MD, Susanne Unger, MSc, Hüseyin.

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Presentation on theme: "Β2-Microglobulin deficiency causes a complex immunodeficiency of the innate and adaptive immune system  Ömür Ardeniz, MD, Susanne Unger, MSc, Hüseyin."— Presentation transcript:

1 β2-Microglobulin deficiency causes a complex immunodeficiency of the innate and adaptive immune system  Ömür Ardeniz, MD, Susanne Unger, MSc, Hüseyin Onay, MD, PhD, Sandra Ammann, MSc, Caroline Keck, MSc, Corina Cianga, MD, PhD, Bengü Gerçeker, MD, Bianca Martin, PhD, Ilka Fuchs, MSc, Ulrich Salzer, MD, Aydan İkincioğulları, MD, Deniz Güloğlu, PhD, Tuğrul Dereli, MD, Robert Thimme, MD, Stephan Ehl, MD, Klaus Schwarz, MD, Annette Schmitt-Graeff, MD, Petru Cianga, MD, PhD, Paul Fisch, MD, Klaus Warnatz, MD  Journal of Allergy and Clinical Immunology  Volume 136, Issue 2, Pages (August 2015) DOI: /j.jaci Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 A, Clinical presentation, pedigree, and molecular characterization of β2m deficiency. A-C, Midface destruction (Fig 1, A), skin lesions (Fig 1, B), and bronchiectasis (Fig 1, C) in patient IV-7 (P1). D, Pedigree of the index patient. IV-10 (P2) is the younger brother. E, Both had a homozygous mutation in intron 1 (c.67+1G>T). F, Abrogating full-length mRNA expression, as shown by RT-PCR. GAPDH, Glyceraldehyde-3-phosphate dehydrogenase. G, β2m protein was absent on the surfaces of patients' CD45+ lymphocytes. FMO, Fluorescence Minus One; T control, transport control. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Expression of β2m-associated proteins in patients with β2m deficiency. A, Surface HLA-A, HLA-B, and HLA-C expression on CD45+ lymphocytes. B, Expression of MHC-I α-chains bound to β2m (B and Q1/28) and unbound (HC10). C, Intraepithelial CD1a+ Langerhans cells in the skin of P2 and a control subject. D, Surface expression of CD1a, CD1b, and CD1c on monocyte-derived dendritic cells and of CD1d on monocytes. E and F, FcRn surface expression on monocytes (Fig 1, E) and in the skin (Fig 1, F). FMO, Fluorescence Minus One; T control, transport control. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 T-cell compartment in patients with β2m deficiency. A, Distribution of CD4, CD8, and γδ T cells gated on CD3+ T cells. B, Phenotyping of TCRαβ+ CD8 T cells. NA, Not available. C, Vα24+Vβ11+ NKT cells gated on lymphocytes. D, Phenotyping of CD8+ γδ T cells. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Cytotoxicity in patients with β2m deficiency. A, Perforin expression in CD3+CD4+CD8− T cells. B, Degranulation of CD8 T-cell blasts. C and D, Degranulation (Fig 4, C) and killing (Fig 4, D) of target K562 cells by NK cells. T control, Transport control. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Inflammatory skin changes in patients with β2m deficiency. A-H, Characteristic morphologic features of a skin biopsy specimen of P1 adjacent to a florid ulcerated lesion. Fig 5, A, Dense fibrosis involving the dermis and subcutaneous tissue accompanied by a reduction in hair follicles and sweat glands. Fig 5, B, Discrete perivascular CD4+ infiltrates in the superficial dermis. Fig 5, C, Predominantly CD8+ intraepithelial lymphocytes. Fig 5, D, Presence of γδ T cells occasionally forming small intraepithelial clusters (arrowhead). Fig 5, E-H, Granulomatous lesions in the deep fibrotic dermis (Fig 5, E and F, arrows) comprising numerous CD68+ macrophages, scattered giant cells (Fig 5, G, asterisk), and rare perforin-positive cytotoxic T cells (Fig 5, H). I-L, Fibrotic skin (Fig 5, I) from P2 developing focal granulomatous CD4+ inflammatory lesions (Fig 5, J) characterized by a high content of mononuclear CD68+ macrophages (Fig 5, K) and CD8+ T cells (Fig 5, L) but without evidence of giant cells. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig E1 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig E2 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Fig E3 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

10 Fig E4 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

11 Fig E5 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

12 Fig E6 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

13 Fig E7 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

14 Fig E8 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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