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Mucosal Immunol. 2016 Jan;9(1):254-64. doi: 10.1038/mi.2015.57. Epub 2015 Jul 8.

Responsive population dynamics and wide seeding into the duodenal lamina propria of transglutaminase-2-specific plasma cells in celiac disease.

Author information

1
Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
2
Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.
3
Departments of Internal Medicine and Gastroenterology, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland.
4
Bioengineering Program, Faculty of Engineering, Bar-Ilan University, Ramat Gan, Israel.
5
Centre for Immune Regulation and Department of Gastroenterology, Oslo University Hospital-Rikshospitalet, Oslo, Norway.
6
Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut, USA.
7
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
8
Immunology Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
9
Tampere Centre for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland.

Abstract

A hallmark of celiac disease is autoantibodies to transglutaminase 2 (TG2). By visualizing TG2-specific antibodies by antigen staining of affected gut tissue, we identified TG2-specific plasma cells in the lamina propria as well as antibodies in the subepithelial layer, inside the epithelium, and at the brush border. The frequency of TG2-specific plasma cells were found not to correlate with serum antibody titers, suggesting that antibody production at other sites may contribute to serum antibody levels. Upon commencement of a gluten-free diet, the frequency of TG2-specific plasma cells in the lesion dropped dramatically within 6 months, yet some cells remained. The frequency of TG2-specific plasma cells in the celiac lesion is thus dynamically regulated in response to gluten exposure. Laser microdissection of plasma cell patches, followed by antibody gene sequencing, demonstrated that clonal cells were seeded in distinct areas of the mucosa. This was confirmed by immunoglobulin heavy chain repertoire analysis of plasma cells isolated from individual biopsies of two untreated patients, both for TG2-specific and non-TG2-specific cells. Our results shed new light on the processes underlying the B-cell response in celiac disease, and the approach of staining for antigen-specific antibodies should be applicable to other antibody-mediated diseases.

PMID:
26153762
PMCID:
PMC4703456
DOI:
10.1038/mi.2015.57
[Indexed for MEDLINE]
Free PMC Article

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