title: Fate of five celiac disease-associated antibodies during normal diet in genetically at-risk children observed from birth in a natural history study.
abstract: OBJECTIVE
  To explore the natural history of antibodies against tissue transglutaminase (TGA), endomysium (EMA), reticulin (ARA), and gliadin (AGA-IgG and AGA-IgA) in children carrying HLA-conferred risk for celiac disease (CD) and observed frequently from birth.
  
  
  METHODS
  TGA was measured in serum samples obtained between years 2000 and 2003 from 1,320 children carrying genetic CD risk. If a sample was TGA positive, all five antibodies were analyzed in all banked and forthcoming samples from that child, and a duodenal biopsy was recommended. At the end of this observation, in August 2004, the age of the children was from 1 to 9.5 yr (mean 4.1 yr).
  
  
  RESULTS
  Forty-nine children (3.7%) were TGA positive. In these children, AGA-IgG had emerged at the mean age (+/- SD, range) of 2.0 +/- 1.5, 0.5-6.6 yr, while TGA, EMA, and ARA all emerged concurrently somewhat later (TGA at 3.2 +/- 1.5, 1.0-7.0 yr, P < 0.001 when compared to AGA-IgG). Despite continuing gluten exposure, positive TGA, EMA, ARA, AGA-IgA, and AGA-IgG values were spontaneously lost in 49%, 45%, 43%, 41%, and 32% of the children, respectively. CD was diagnosed by biopsy in 20 of the 26 TGA-positive children who consented to a biopsy.
  
  
  CONCLUSIONS
  Potential CD trigger(s) other than only gluten probably function before AGA-IgG emerges, i.e., > or =3 months earlier than the transglutaminase-associated antibodies appear. In a remarkable proportion of the children, antibodies disappear spontaneously suggesting that regulatory immune phenomena under favorable circumstances are able to extinguish incipient CD in genetically at-risk children even without exclusion of gluten from the diet.
authors.affiliation: JDRF Center for Prevention of Type 1 Diabetes in Finland, and Department of Pediatrics, University of Turku, Turku, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Simell
authors.forename: Sanna
authors.initials: S
authors.lastname: Hoppu
authors.forename: Anne
authors.initials: A
authors.lastname: Hekkala
authors.forename: Tuula
authors.initials: T
authors.lastname: Simell
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Ståhlberg
authors.forename: Markku
authors.initials: M
authors.lastname: Viander
authors.forename: Heta
authors.initials: H
authors.lastname: Yrjänäinen
authors.forename: Juhani
authors.initials: J
authors.lastname: Grönlund
authors.forename: Perttu
authors.initials: P
authors.lastname: Markula
authors.forename: Ville
authors.initials: V
authors.lastname: Simell
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Heikki
authors.initials: H
authors.lastname: Hyöty
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D001707:Biopsy, Needle; D002446:Celiac Disease / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004032:Diet; D020022:Genetic Predisposition to Disease; D005903:Gliadin / Q000276:immunology; D005983:Glutens / Q000008:administration & dosage; D015234:HLA-A Antigens / Q000032:analysis; D006801:Humans; D007223:Infant; D007422:Intestines / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000276:immunology; D012155:Reticulin / Q000276:immunology; D011503:Transglutaminases / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015234:HLA-A Antigens; D012155:Reticulin; D005983:Glutens; D005903:Gliadin; D011503:Transglutaminases