By David Douglas
NEW YORK (Reuters Health) - In high-risk children, co-occurrence of autoimmunity to type 1 diabetes and celiac disease is higher than would be expected in the general population, according to a large, prospective birth cohort study.
The international Environmental Determinants of Diabetes in Youth (TEDDY) Consortium focuses on “children at high HLA risk of both type 1 diabetes (T1D) and celiac disease (CD),” lead author Dr. William Hagopian of Pacific Northwest Research Institute, in Seattle, told Reuters Health by email.
"Using specific autoantibodies as early markers of each disease, it was possible to investigate the early interrelationship of the two autoimmunities from immunological, genetic, and demographic perspectives," he said.
According to an October 10 online report in Pediatrics, Dr. Hagopian and colleagues analyzed data from 5,891 children at high genetic risk of both T1D and CD, reflected in gene analyses done by 4.5 months of age. The children were repeatedly evaluated for persistent islet autoantibodies (IAs), tissue transglutaminase autoantibodies (tTGAs), and other factors. Median follow-up was 5.5 years.
Overall, IAs alone were identified in 367 children (6.2%) and tTGAs alone in 808 (13.7%). IAs preceding tTGAs were associated with a significantly increased risk of tTGAs (hazard ratio, 1.48).
Ninety children (1.53%) had both autoantibodies. The researchers calculated that the expected prevalence of having both antibodies in the general population would be 1.19% - a statistically significant 0.34% excess.
After adjustment for sex, country, and other pertinent factors, co-occurrence of the two markers was significantly greater in children with a family history of T1D (HR, 2.80), those with HLA-DR3/4 genotypes (HR, 1.94), and those with the single-nucleotide polymorphism rs3184504 at SH2B3 (HR, 1.53).
However, say the researchers, the "observed co-occurrence was not fully accounted for by all analyzed factors,” also noting that "shared environmental or pathophysiological mechanisms may contribute to the increased risk."
"Elucidation of relevant mechanisms," they add, "will require additional studies of local immune responses as well as common exposures."
Nevertheless, Dr. Hagopian concluded, "Our results suggest that even islet autoantibody-positive children at high risk of subsequently developing clinical disease, and not just those with a confirmed diagnosis of T1D, should be screened for CD."
In an accompanying editorial, Drs. Christine T. Ferrara and Stephen E. Gitelman of the University of California at San Francisco caution that "although the results from the TEDDY study are hypothesis-generating, they do not directly establish causality."
"The current TEDDY study contributes to the hypothesis that initial autoimmunity triggered against 1 organ may potentiate additional autoimmune diseases,” they write, noting that future research into risk factors and mechanisms may help to identify “modifiable novel drug targets with the potential to prevent 1 or more autoimmune diseases.”
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