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Transglutaminase 2-specific Celiac Antibodies Trigger Changes and Signs of Inflammation in Mice

Transglutaminase 2-specific celiac disease autoantibodies cause bowel changes in mice.


Photo: CC--Aini

Celiac.com 11/04/2016 - Patients in the earliest stages of celiac disease have TG2-autoantibodies present in serum and small-intestinal mucosa. Many suffer abdominal symptoms long before the development of villus atrophy.

The classic small-bowel mucosal damage that marks celiac disease develops over time and in stages; from normal villi to inflammation and finally to villus atrophy with crypt hyperplasia. Previously, researchers have shown that intraperitoneal injections of sera from celiac patients or of purified immunoglobulin fraction into mice trigger a condition mimics early-stage celiac disease.

Those same researchers recently set out to show whether re-combinantly produced, patient-derived TG2-targeted autoantibodies are alone sufficient to trigger such condition in immune-compromised mice. The research team included Suvi Kalliokoski, Victoria Ortín Piqueras, Rafael Frías, Ana-Marija Sulic, Juha A. E. Määttä, Niklas Kähkönen, Keijo Viiri, Heini Huhtala, Arja Pasternack, Kaija Laurila, Daniele Sblattero, Ilma R. Korponay-Szabó, Markku Mäki, Sergio Caja, Katri Kaukinen, Katri Lindfors.

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They are various affiliated with the Tampere Center for Child Health Research, the Tampere School of Health Sciences, the Department of Internal Medicine, with BioMediTech at Tampere University Hospital and School of Medicine at the University of Tampere in Tampere, Finland, with the Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, and Department of Bacteriology and Immunology at the University of Helsinki in Helsinki, Finland, with the Central Animal Laboratory at the University of Turku in Turku, Finland, with the Comparative Medicine Karolinska Institutet in Stockholm, Sweden, with the Department of Life Sciences at the University of Trieste in Trieste, Italy, and with the Celiac Disease Center, Medical and Health Science Center, Heim Pál Children’s Hospital and Department of Pediatrics at the University of Debrecen in Debrecen, Hungary.

Interestingly, mice injected with celiac patient TG2-antibodies showed changes to small-intestinal mucosa, increased lamina propria cellular infiltration and disease-specific autoantibodies in the small bowel, but did not show any clinical signs of celiac disease.

Thus, celiac patient-derived TG2-specific autoantibodies seem to be enough to trigger small-bowel mucosal changes in mice, but probably not enough to trigger clinical features on their own. Triggering clinical celiac features likely requires other factors, such as other antibody populations implicated in celiac disease.

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