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Transglutaminase 2-specific coeliac disease autoantibodies induce morphological changes and signs of inflammation in the small-bowel mucosa of mice

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Abstract

Coeliac disease is hallmarked by an abnormal immune reaction against ingested wheat-, rye- and barley-derived gluten and the presence of transglutaminase 2 (TG2)-targeted autoantibodies. The small-bowel mucosal damage characteristic of the disorder develops gradually from normal villus morphology to inflammation and finally to villus atrophy with crypt hyperplasia. Patients with early-stage coeliac disease have TG2-autoantibodies present in serum and small-intestinal mucosa and they may already suffer from abdominal symptoms before the development of villus atrophy. Previously, we have shown that intraperitoneal injections of coeliac patient-derived sera or purified immunoglobulin fraction into mice induce a condition mimicking early-stage coeliac disease. In the current study, we sought to establish whether recombinantly produced patient-derived TG2-targeted autoantibodies are by themselves sufficient for the development of such an experimentally induced condition in immune-compromised mice. Interestingly, mice injected with coeliac patient TG2-antibodies had altered small-intestinal mucosal morphology, increased lamina propria cellular infiltration and disease-specific autoantibodies deposited in the small bowel, but did not evince clinical features of the disease. Thus, coeliac patient-derived TG2-specific autoantibodies seem to be sufficient for the induction of subtle small-bowel mucosal alterations in mice, but the development of clinical features probably requires additional factors such as other antibody populations relevant in coeliac disease.

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Acknowledgments

This work was supported by funding from the Academy of Finland Research Council for Health, the Competitive State Research Financing of the Expert Responsibility Areas of Tampere University Hospital (Grants 9P060, 9R018, 9S020, 9R034, 9T018, 9T040), the Sigrid Juselius Foundation, the Finnish Cultural Foundation and the Päivikki and Sakari Sohlberg Foundation. Access to the facilities and expertise of the BioMediTech Protein Technologies core facility, a member of Biocenter Finland and Instruct-FI, is gratefully acknowledged. Anne Heimonen, Soili Peltomäki, Jorma Kulmala and Matti Kannisto are thanked for technical assistance.

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Authors and Affiliations

  1. Tampere Center for Child Health Research, School of Medicine, University of Tampere and Tampere University Hospital, PL 100, 33014, Tampere, Finland

    Suvi Kalliokoski, Ana-Marija Sulic, Keijo Viiri, Kaija Laurila, Ilma R. Korponay-Szabó, Markku Mäki, Sergio Caja & Katri Lindfors

  2. Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00014, Helsinki, Finland

    Victoria Ortín Piqueras

  3. Central Animal Laboratory, University of Turku, 20520, Turku, Finland

    Victoria Ortín Piqueras & Rafael Frías

  4. Comparative Medicine, Karolinska Institutet, 17177, Stockholm, Sweden

    Rafael Frías

  5. BioMediTech, University of Tampere, 33014, Tampere, Finland

    Juha A. E. Määttä & Niklas Kähkönen

  6. Tampere School of Health Sciences, University of Tampere, 33014, Tampere, Finland

    Heini Huhtala

  7. Department of Bacteriology and Immunology, University of Helsinki, 00014, Helsinki, Finland

    Arja Pasternack

  8. Department of Life Sciences, University of Trieste, 34100, Trieste, Italy

    Daniele Sblattero

  9. Coeliac Disease Center, Medical and Health Science Center, Heim Pál Children’s Hospital and Department of Pediatrics, University of Debrecen, 4032, Debrecen, Hungary

    Ilma R. Korponay-Szabó

  10. Department of Internal Medicine at Tampere University Hospital and School of Medicine, University of Tampere, 33014, Tampere, Finland

    Katri Kaukinen

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  1. Suvi Kalliokoski
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Correspondence to Suvi Kalliokoski.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any data from studies involving human participants performed by any of the authors.

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Kalliokoski, S., Piqueras, V.O., Frías, R. et al. Transglutaminase 2-specific coeliac disease autoantibodies induce morphological changes and signs of inflammation in the small-bowel mucosa of mice. Amino Acids 49, 529–540 (2017). https://doi.org/10.1007/s00726-016-2306-0

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