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Granuloma-in-follicles in pediatric Crohn’s disease


SNPs in NOD2 are a major susceptibility factor for Crohn’s disease (CD). (Sub)mucosal granulomas are a diagnostic feature of CD.


To better describe morphological and immunohistochemical featurs of pediatric CD (pCD) granulomas.


17 pCD patients with granulomas were genotyped for CD-associated mutations or polymorphisms in NOD2 and autophagy-related genes ATG1 and ATG16L1. Granulomas were found in intestinal biopsies of 22 out of 83 endoscopic and 9 out of 12 surgical procedures. Of each procedure we selected one biopsy per organ to study the cellular composition and cytokine profile of granulomas. We stained 43 paraffin-embedded, formalin-fixed pCD biopsies with hematoxylin&eosin and monoclonal antibodies targeting leukocyte markers (HLA-DR, CD68, CD4, CD8, CD20, IL23R) and cytokines (TNFα, IFNγ, IL6, IL10, IL17, TGFβ) (Figure 1) Morphology and immunohistochemistry were scored semi-quantitatively.

figure 1

Figure 1


In addition to small isolated (sub)mucosal granulomas, we found granulomas in the follicle(GIF) centre of mucosa-associated lymphoid tissue, visualized by CD20 staining (fig). GIF were found in half the number of procedures (more often in chirurgical than in endoscopic) in only 7 out of 17 pCD patients. Exceptional lymphocyte emperipolesis in multinucleated giant cells (MGCs) and IL-17 expression were observed, only in granulomas of pCD with GIF (fig). The granulomas of patients with GIF often had a lymphocytic corona, but polycyclic granuloma architecture was rare. No clear relation was seen between the presence of GIF and the CD-associated NOD2, ATG1 and ATG16L1 genotypes.


We defined GIF as a morphological characteristic in few selected pCD patients, and demonstrate association with emperipolesis of lymphocytes in MGCs and weak IL17 expression.

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Correspondence to Carl EI Janssen.

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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Janssen, C.E., Cleynen, I., De Hertogh, G. et al. Granuloma-in-follicles in pediatric Crohn’s disease. Pediatr Rheumatol 9 (Suppl 1), P294 (2011).

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