Document Detail


Morphologic and immunohistochemical characterization of granulomas in the nucleotide oligomerization domain 2-related disorders Blau syndrome and Crohn disease.
MedLine Citation:
PMID:  22464675     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: Blau syndrome (BS) and Crohn disease (CD) are both characterized by granulomatous inflammation and related to nucleotide oligomerization domain 2 (NOD2) mutations.
OBJECTIVE: This study aimed to define the morphologic and immunohistochemical characteristics of granulomas in patients with NOD2-related BS and CD.
METHODS: Granuloma-containing biopsy specimens from 6 patients with BS and 7 pediatric patients with CD carrying NOD2 mutations or single nucleotide polymorphisms were studied for morphology, cellular composition, and cytokine expression by using hematoxylin and eosin staining and immunohistochemistry.
RESULTS: Biopsy specimens from patients with BS typically showed polycyclic granulomas with large lymphocytic coronas, extensive emperipolesis of lymphocytes within multinucleated giant cells (MGCs), MGC death, and fibrinoid necrosis and fibrosis. In contrast, biopsy specimens from patients with CD showed simple granulomas with subtle/absent lymphocytic coronas, sclerosis of the surrounding tissue, and polymorphonuclear cells. Findings found to be similar in all granulomas were as follows: CD68 and HLA-DR expression by epithelioid cells, monocyte-macrophage lineage cells and MGCs, increased lymphocytic HLA-DR expression, increased CD4(+)/CD8(+) T-cell ratio, and CD20(+) B lymphocytes evenly distributed within and around granulomas. In both patient groups prominent IFN-γ expression was found in and around granulomas, and TNF-α and IL-23 receptor expression was moderate. IL-6, IL-17, and TGF-β expression was prominent in granulomas from patients with BS but sporadic in granulomas from patients with CD. IL-10 expression was absent.
CONCLUSION: Granulomas from patients with BS and granulomas from patients with NOD2-associated CD show distinct morphologic features and cytokine expression patterns, suggesting that the T(H)17 axis might be involved in the pathogenesis of BS, whereas T(H)1 is important in both patients with BS and patients with CD.
Authors:
Carl E I Janssen; Carlos D Rose; Gert De Hertogh; Tammy M Martin; Brigitte Bader Meunier; Rolando Cimaz; Miroslav Harjacek; Pierre Quartier; Rebecca Ten Cate; Caroline Thomee; Valeer J Desmet; Alain Fischer; Tania Roskams; Carine H Wouters
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  129     ISSN:  1097-6825     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1076-84     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Affiliation:
Department of Pediatric Rheumatology, University Hospital Leuven, Leuven, Belgium; Department of Pathology, University Hospital Leuven, Leuven, Belgium.
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