title: Transglutaminase 2-specific coeliac disease autoantibodies induce morphological changes and signs of inflammation in the small-bowel mucosa of mice.
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.
authors: Tampere Center for Child Health Research, School of Medicine, University of Tampere and Tampere University Hospital, PL 100, 33014, Tampere, Finland. suvi.kalliokoski@uta.fi.
authors: Suvi
authors: 0000-0003-2934-3077
authors: S
authors: Kalliokoski
authors: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00014, Helsinki, Finland.|Central Animal Laboratory, University of Turku, 20520, Turku, Finland.
authors: Victoria Ortín
authors: VO
authors: Piqueras
authors: Central Animal Laboratory, University of Turku, 20520, Turku, Finland.|Comparative Medicine, Karolinska Institutet, 17177, Stockholm, Sweden.
authors: Rafael
authors: R
authors: Frías
authors: Tampere Center for Child Health Research, School of Medicine, University of Tampere and Tampere University Hospital, PL 100, 33014, Tampere, Finland.
authors: Ana-Marija
authors: AM
authors: Sulic
authors: BioMediTech, University of Tampere, 33014, Tampere, Finland.
authors: Juha A E
authors: JA
authors: Määttä
authors: BioMediTech, University of Tampere, 33014, Tampere, Finland.
authors: Niklas
authors: N
authors: Kähkönen
authors: Tampere Center for Child Health Research, School of Medicine, University of Tampere and Tampere University Hospital, PL 100, 33014, Tampere, Finland.
authors: Keijo
authors: K
authors: Viiri
authors: Tampere School of Health Sciences, University of Tampere, 33014, Tampere, Finland.
authors: Heini
authors: H
authors: Huhtala
authors: Department of Bacteriology and Immunology, University of Helsinki, 00014, Helsinki, Finland.
authors: Arja
authors: A
authors: Pasternack
authors: Tampere Center for Child Health Research, School of Medicine, University of Tampere and Tampere University Hospital, PL 100, 33014, Tampere, Finland.
authors: Kaija
authors: K
authors: Laurila
authors: Department of Life Sciences, University of Trieste, 34100, Trieste, Italy.
authors: Daniele
authors: D
authors: Sblattero
authors: Tampere Center for Child Health Research, School of Medicine, University of Tampere and Tampere University Hospital, PL 100, 33014, Tampere, Finland.|Coeliac Disease Center, Medical and Health Science Center, Heim Pál Children's Hospital and Department of Pediatrics, University of Debrecen, 4032, Debrecen, Hungary.
authors: Ilma R
authors: IR
authors: Korponay-Szabó
authors: Tampere Center for Child Health Research, School of Medicine, University of Tampere and Tampere University Hospital, PL 100, 33014, Tampere, Finland.
authors: Markku
authors: M
authors: Mäki
authors: Tampere Center for Child Health Research, School of Medicine, University of Tampere and Tampere University Hospital, PL 100, 33014, Tampere, Finland.
authors: Sergio
authors: S
authors: Caja
authors: Department of Internal Medicine at Tampere University Hospital and School of Medicine, University of Tampere, 33014, Tampere, Finland.
authors: Katri
authors: K
authors: Kaukinen
authors: Tampere Center for Child Health Research, School of Medicine, University of Tampere and Tampere University Hospital, PL 100, 33014, Tampere, Finland.
authors: Katri
authors: K
authors: Lindfors
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D001323:Autoantibodies / Q000096:biosynthesis*; D016466:CHO Cells; D002446:Celiac Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003412:Cricetulus; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D005983:Glutens / Q000737:chemistry / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host; D007070:Immunoglobulin A / Q000096:biosynthesis; D007150:Immunohistochemistry; D007249:Inflammation; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D011503:Transglutaminases / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007070:Immunoglobulin A; D011994:Recombinant Proteins; D005983:Glutens; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Cellular infiltration; Cytokine; Intestinal autoantibody deposits; Intestinal permeability; Small-intestinal morphology