Abstract
Typical features of celiac disease are small-bowel villus atrophy, crypt hyperplasia, and inflammation which develop gradually concomitant with ingestion of gluten. In addition, patients have anti-transglutaminase 2 (TG2) autoantibodies in their serum and tissues. The aim of this study was to establish whether celiac disease can be passively transferred to mice by serum or immunoglobulins. Serum aliquots or purified immunoglobulins (Ig) were intraperitoneally injected into Hsd:Athymic Nude-Foxn1nu mice for 8 or 27 days. As mice do not have proper IgA transport from peritoneum to blood, sera with a high content of IgG class anti-TG2 antibodies from untreated IgA-deficient celiac patients were used. Mouse sera were tested for celiac disease-specific autoantibodies, and several tissues were analyzed for autoantibody deposits targeted to TG2. Morphological assessment was made of the murine small intestinal mucosa. Injection of celiac disease patient sera or total IgG led to a significant delay in weight gain and mild diarrhea in a subset of mice. The mice injected with celiac patient sera or IgG had significantly decreased villus height crypt depth (Vh/CrD) ratios and celiac disease-specific autoantibody deposits targeted to TG2 in several tissues, including the small intestine. None of these features were observed in control mice. We conclude that administration of IgA-deficient celiac disease patient serum or total IgG induces both deterioration of the intestinal mucosa and clinical features of celiac disease in mice. The experimentally induced condition in the mice injected with patient serum or IgG resembles early developing celiac disease in humans.
Key message
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Celiac disease patient sera or total IgG was injected into athymic mice.
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A significant delay in weight gain and mild diarrhea was observed.
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Mice evinced significantly decreased villus height crypt depth ratios.
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Celiac disease-specific autoantibody deposits were present in several tissues.
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The condition in mice resembles early stage celiac disease in humans.
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Acknowledgments
This work was supported by grants to the Celiac Disease Study Group from the University of Tampere, the Academy of Finland, the Sigrid Juselius Foundation, the Competitive State Research Financing of the Expert Area of Tampere University Hospital (grants 9R034 and 9R018) and Seinäjoki Central Hospital (VTR16), the Research Fund of the Finnish Coeliac Society, the Finnish Cultural Foundation, the Hungarian Scientific Research Fund (OTKA K101788), TÁMOP 4.2.2.A-11/1/KONV-2012-0023 VED-ELEM, and the European Commission (contract number PIA-GA-2010-251506).
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The authors declare no conflict of interests related to this study.
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Kalliokoski, S., Caja, S., Frias, R. et al. Injection of celiac disease patient sera or immunoglobulins to mice reproduces a condition mimicking early developing celiac disease. J Mol Med 93, 51–62 (2015). https://doi.org/10.1007/s00109-014-1204-8
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DOI: https://doi.org/10.1007/s00109-014-1204-8