title: Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?
abstract: Two common chronic childhood diseases-celiac disease (CD) and type 1 diabetes (T1D)-result from complex pathological mechanisms where genetic susceptibility, environmental exposure, alterations in intestinal permeability and immune responses play central roles. In this study, we investigated whether these characteristics were universal for CD independently of T1D association. For this purpose, we studied 36 children with normal small-bowel mucosa and 26 children with active CD, including 12 patients with T1D. In samples from the small-bowel mucosa, we detected the lowest expression of tight junction protein 1 (TJP1) mRNA in CD patients with T1D, indicating an increase in intestinal permeability. Furthermore, these samples displayed the highest expression of forkhead box P3 (FoxP3) mRNA, a marker for regulatory T cells, as compared with other patient groups. At the same time, serum levels of IgA antibodies specific for the CD-related antigens deamidated gliadin and tissue transglutaminase (tTG) were the highest in CD patients with T1D. In contrast, no significant differences were found in IgA or IgG antibodies specific for bovine beta-lactoglobulin or Bifidobacterium adolescentis DSM 20083-derived proteins. There were also no differences in the transamidating activity of serum autoantibodies between patients and control individuals. Our results show that patients with T1D and newly detected CD exhibit severely altered intestinal permeability, strong local immune activation and increased immunoregulatory mechanisms in the small bowel. Further study is required to determine whether these extreme changes in this CD subgroup are due to some specific environmental factors (virus infections), unknown genetic effects or autoimmune reactions to antigenic targets in intracellular tight junctions.
authors.affiliation: Department of Immunology, University of Tartu, Tartu, Estonia. raivo.uibo@ut.ee
authors.forename: Raivo
authors.initials: R
authors.lastname: Uibo
authors.forename: Marina
authors.initials: M
authors.lastname: Panarina
authors.forename: Kaupo
authors.initials: K
authors.lastname: Teesalu
authors.forename: Ija
authors.initials: I
authors.lastname: Talja
authors.forename: Epp
authors.initials: E
authors.lastname: Sepp
authors.forename: Meeme
authors.initials: M
authors.lastname: Utt
authors.forename: Marika
authors.initials: M
authors.lastname: Mikelsaar
authors.forename: Kaire
authors.initials: K
authors.lastname: Heilman
authors.forename: Oivi
authors.initials: O
authors.lastname: Uibo
authors.forename: Tamara
authors.initials: T
authors.lastname: Vorobjova
mesh_terms: D000293:Adolescent; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D001644:Bifidobacterium / Q000276:immunology; D002417:Cattle; D002446:Celiac Disease / Q000150:complications* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005903:Gliadin / Q000276:immunology; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology; D007422:Intestines / Q000276:immunology* / Q000473:pathology*; D007782:Lactoglobulins / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007782:Lactoglobulins; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins