Fate of five celiac disease-associated antibodies during normal diet in genetically at-risk children observed from birth in a natural history study.
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.
Simell
Satu
S
JDRF Center for Prevention of Type 1 Diabetes in Finland, and Department of Pediatrics, University of Turku, Turku, Finland.
Hoppu
Sanna
S
Hekkala
Anne
A
Simell
Tuula
T
Ståhlberg
Marja-Riitta
MR
Viander
Markku
M
Yrjänäinen
Heta
H
Grönlund
Juhani
J
Markula
Perttu
P
Simell
Ville
V
Knip
Mikael
M
Ilonen
Jorma
J
Hyöty
Heikki
H
Simell
Olli
O
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
D001323:Autoantibodies; D015234:HLA-A Antigens; D012155:Reticulin; D005983:Glutens; D005903:Gliadin; D011503:Transglutaminases