Morphologic and immunohistochemical characterization of granulomas in the nucleotide oligomerization domain 2–related disorders Blau syndrome and Crohn.

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Morphologic and immunohistochemical characterization of granulomas in the nucleotide oligomerization domain 2–related disorders Blau syndrome and Crohn disease Carl E.I. Janssen, MBMS, Carlos D. Rose, MD, CIP, Gert De Hertogh, MD, PhD, Tammy M. Martin, PhD, Brigitte Bader Meunier, MD, Rolando Cimaz, MD, Miroslav Harjacek, MD, Pierre Quartier, MD, Rebecca Ten Cate, MD, Caroline Thomee, MD, Valeer J. Desmet, MD, PhD, Alain Fischer, MD, PhD, Tania Roskams, MD, PhD, Carine H. Wouters, MD, PhD Journal of Allergy and Clinical Immunology Volume 129, Issue 4, Pages 1076-1084 (April 2012) DOI: 10.1016/j.jaci.2012.02.004 Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Granulomas in patients with BS. A, Hematoxylin and eosin staining of a large polycyclic granuloma with emperipolesis of lymphocytes within MGCs (black arrows; original magnification ×400). B, Hematoxylin and eosin staining of emperipolesis-associated MGC death (original magnification ×400). C, Dense IFN-γ staining within and around a polycyclic granuloma (original magnification ×200). D, Dense IL-6 staining as in Fig 1, C (original magnification ×200). E, Moderate TGF-β staining of intragranulomatous lymphocytes close to a small MGC with emperipolesis (black arrow; original magnification ×400). F, Dense IL-17 staining within and around a polycyclic granuloma (original magnification ×200). Images were acquired with a Leica DMLB 11888011 microscope (Leica Microsystems, Wetzlar, Germany; objective lenses ×5, ×10, ×20, ×40, and ×100). The digital camera was a Leica DC 300 V2.0 10447117 (Leica Microsystems AG), and image processing was done with Leica IM50 Image Manager. Journal of Allergy and Clinical Immunology 2012 129, 1076-1084DOI: (10.1016/j.jaci.2012.02.004) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Granulomas in patients with NOD2-associated CD. A, Hematoxylin and eosin staining of a small isolated granuloma (original magnification ×400). B, Hematoxylin and eosin staining of eosinophils (black arrows) and sclerosis of surrounding tissue (original magnification ×400). C, Dense TNF-α staining of a granuloma (original magnification ×400). D, Mild TGF-β staining of lymphocytes around a granuloma with an MGC exhibiting mild emperipolesis (black arrow) and a crystalline inclusion (gray arrow; original magnification ×400). E and F, Moderate IL-23R staining (original magnification ×400; Fig 2, E) and exceptional IL-17 staining of a GIF in the mucosa-associated lymphoid tissue of the colon (original magnification ×200; Fig 2, F). Images were acquired as described in Fig 1. Journal of Allergy and Clinical Immunology 2012 129, 1076-1084DOI: (10.1016/j.jaci.2012.02.004) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Granulomas in patients with BS. A, HLA-DR staining of a large polycyclic granuloma in the spleen of case 5 (original magnification ×200). B, CD68 staining visualizes MML cells. (original magnification ×200). C, CD4 staining shows a dense corona of lymphocytes surrounding the granuloma (original magnification ×200). D, CD8 staining shows few CD8+ lymphocytes in and around the granuloma (original magnification ×200). Images were acquired as described in Fig 1. Journal of Allergy and Clinical Immunology 2012 129, 1076-1084DOI: (10.1016/j.jaci.2012.02.004) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions