Abstract | BACKGROUND: 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.
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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 |
Journal | The Journal of allergy and clinical immunology
(J Allergy Clin Immunol)
Vol. 129
Issue 4
Pg. 1076-84
(Apr 2012)
ISSN: 1097-6825 [Electronic] United States |
PMID | 22464675
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved. |
Chemical References |
- Cytokines
- NOD2 protein, human
- Nod2 Signaling Adaptor Protein
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Topics |
- Adolescent
- Arthritis
- Child
- Child, Preschool
- Cranial Nerve Diseases
(genetics, metabolism, pathology)
- Crohn Disease
(genetics, immunology, pathology)
- Cytokines
(metabolism)
- Female
- Granuloma
(genetics, immunology, pathology)
- Humans
- Immunohistochemistry
- Infant
- Male
- Mutation
- Nod2 Signaling Adaptor Protein
(genetics, immunology)
- Sarcoidosis
- Synovitis
(genetics, metabolism, pathology)
- Uveitis
(genetics, metabolism, pathology)
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