Natural history of transglutaminase autoantibodies and mucosal changes in children carrying HLA-conferred celiac disease susceptibility.
OBJECTIVE
The natural history of the appearance and fate of transglutaminase autoantibodies (TGAs) and mucosal changes in children carrying HLA-conferred celiac disease (CD) risk remains obscure. The aim of this study was to investigate the sequence of events leading to overt CD by retrospective analysis of TGA values in serum samples collected frequently from genetically susceptible children since birth or early childhood.


METHODS
A total of 1101 at-risk children were recruited in the study. A duodenal biopsy was recommended to all TGA-positive children and performed if parental consent was obtained.


RESULTS
During up to 8 years of follow-up, 35 of the cohort children developed TGAs, the youngest at age 1.3 years. After age 1.3 years the annual TGA seroconversion rate was constantly around 1% at least until age 6 years. However, 18 of the 35 TGA-positive children (51%) lost TGAs, without any dietary manipulation. A further 7 children were IgA deficient; of these children, 2 developed IgG antigliadin antibodies (IgG-AGA). Only 13 of the 21 children (62%) who had duodenal biopsies had villous atrophy. The time that passed since emergence of TGAs failed to predict the biopsy findings. Only one of the children with TGAs and both of the IgA-deficient children with IgG-AGA had noticeable abdominal symptoms.


CONCLUSIONS
TGAs appear in children at a constant rate after 1 year of age until at least the age of 6 years. Over half of the children loose TGA without gluten exclusion, challenging TGA positivity-based CD prevalence estimates. In symptom-free children, a requirement of two consecutive TGA-positive samples taken >or=3 months apart before performing a duodenal biopsy might diminish the number of unnecessary intestinal biopsies.
Simell
Satu
S
The JDRF Center for Prevention of Type I Diabetes in Finland, University of Turku, and Tampere University Hospital, Finland. satu.simell@tyks.fi
Kupila
Antti
A
Hoppu
Sanna
S
Hekkala
Anne
A
Simell
Tuula
T
Ståhlberg
Marja-Riitta
MR
Viander
Markku
M
Hurme
Timo
T
Knip
Mikael
M
Ilonen
Jorma
J
Hyöty
Heikki
H
Simell
Olli
O
D001323:Autoantibodies / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D002446:Celiac Disease / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000517:prevention & control; D004386:Duodenum / Q000378:metabolism / Q000473:pathology; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005903:Gliadin / Q000276:immunology / Q000378:metabolism; D006680:HLA Antigens / Q000378:metabolism*; D006239:Haplotypes; D006801:Humans; D017098:IgA Deficiency / Q000150:complications; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007223:Infant; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D011237:Predictive Value of Tests; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D011503:Transglutaminases / Q000097:blood / Q000276:immunology*
D001323:Autoantibodies; D015415:Biomarkers; D006680:HLA Antigens; D007074:Immunoglobulin G; D005903:Gliadin; D011503:Transglutaminases