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OBJECTIVES: 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., ≥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. [ABSTRACT FROM AUTHOR]

Because celiac disease (CD) is a common partner of type 1 diabetes (T1D), the two diseases may share pathways in pathogenesis. In T1D Prediction and Prevention Study (DIPP) we examined serum samples from over 2000 children with HLA-conferred genetic T1D and CD susceptibility, born between 11/1994 and 12/2002. The samples were collected at 3- to 12-month intervals and examined for antibodies to tissue transglutaminase (TGA). If positive, all previous and forthcoming samples were also examined for endomysium (EMA), reticulin (ARA) and gliadin antibodies (AGA-IgA,AGA-IgG). Eighty one (ca 4%) of the 2000 children were TGA-positive. AGA-IgG emerged first at age 2.2 ± 1.7; 0.5-7.5 years (mean ± SD; range). TGA, EMA and ARA emerged slightly later (TGA at 3.5±1.9; 1.0-9.0 years; p<0.001). Very few TGA-positive children had symptoms of CD; most were symptom-flee. Because a majority of serum samples was collected before this CD study began, the children were continuously exposed to gluten until TGA positivity was retrospectively discovered using biobanked serum samples. Despite continued gluten exposure TGA, EMA, ARA, AGA-IgA and AGA-IgG positivity disappeared spontaneously in 47%, 36%, 37, 43% and 29% of the children, respectively. CD was diagnosed in 42 of 53 TGA positive children whose parents consented to biopsy. In conclusion, potential non-gluten factor(s) regulating onset of CD autoimmunity probably function before AGA-IgG emerges. In a large proportion of children CD-associated antibodies disappear spontaneously suggesting that regulatory immune phenomena often extinguish incipient CD without exclusion of gluten from the diet. [ABSTRACT FROM AUTHOR]

The article discusses a research study which investigated the association of increased risk of pediatric celiac disease with the presence of human leukocyte antigen (HLA) haplotype DR3-DQ2 or DR4-DQ8 disease and serum antibodies against tissue transglutaminase (tTG) among children from the U.S., Finland, Germany and Sweden. Study results provided show the hazard ratios for celiac disease autoimmunity among heterozygotes and homozygotes as compared to children with the lowest-risk genotypes.