Prospective human leukocyte antigen, endomysium immunoglobulin A antibodies, and transglutaminase antibodies testing for celiac disease in children with Down syndrome.

OBJECTIVE: To assess the effect of a prospective screening strategy for the early diagnosis of celiac disease (CD) in children with Down syndrome (DS). STUDY DESIGN: Blood samples were taken from 155 children with DS. Buccal swabs were also taken from 9 of these children for determination of human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 positivity. Independently, immunoglobulin A anti-endomysium-(EMA) and anti-tissue transglutaminase antibodies (TGA) were tested. An intestinal biopsy was performed to confirm the diagnosis of CD. RESULTS: Sixty-three children (40.6%) had test results that were positive for HLA-DQ2 or HLA-DQ8. Results of HLA DQ-typing of DNA isolated from blood and buccal swabs were identical. Eight of the children in whom test results were positive for HLA-DQ2/8 also had positive test results for EMA and TGA. CD was confirmed in 7 of these children with an intestinal biopsy, and in 1 child, CD was suggested with improvement on a gluten-free diet. CONCLUSIONS: We found a prevalence of CD in children with DS of 5.2% (10 times higher than the general Dutch population). We recommend HLA-DQ2/8 typing from buccal swabs in the first year of life and initiating serologic screening of children with DS in whom test results are positive for HLA-DQ2 or DQ8 at age 3 years. Early knowledge of negative HLA-DQ2/8 status can reassure most parents that their children do not have a CD risk.

The IL-1 gene family and bone involvement in celiac disease.

Celiac disease (CD) is associated with decreased bone mineral mass. Its pathogenesis is multifactorial since both systemic and local mechanisms may play a role. Our objective was to determine whether single-nucleotide polymorphisms in genes encoding members of the interleukin-1 family are associated with bone damage measured by densitometry in a series of 71 adult CD patients assessed at diagnosis. When compared with non-carrier CD patients, carriers of allele T of the interleukin-1beta gene (IL1B-511T) had a significantly lower bone mass at the total skeleton level (p = 0.0484) and a greater prevalence of osteopenia/osteoporosis (p = 0.0102). To our knowledge, this is the first evidence on the association between a genetic predisposition and low bone mass in CD patients. This finding supports the postulated inflammation-associated bone loss pathogenesis as one of the causes of bone weakness in CD.

Accuracy and cost-effectiveness of a new strategy to screen for celiac disease in children with Down syndrome.

OBJECTIVES: To investigate the best approach to screen for celiac disease (CD) in patients with Down syndrome (DS). STUDY DESIGN: One hundred thirty-seven children with DS were followed up longitudinally. CD screening was offered in 1994, 1996, and 1999 by determination of serum immunoglobulin A-anti-endomysium antibodies (AEA). The HLA-DQA1*0501/DQB1*02 allelic combination known to be strongly positively associated with CD was typed. All IgA-AEA-positive children were given the opportunity to undergo a small bowel biopsy: if villous atrophy was found, the diagnosis of CD was established. RESULTS: CD was diagnosed in 11 (8%) children: 8 in 1994 and 3 in 1996. All of them carried the HLA-DQ alleles associated with CD. The presence of symptoms was not useful in discriminating which children could have CD. CONCLUSIONS: Screening once in a lifetime is not enough to detect CD in patients with DS. We propose a new, accurate, and cost-sparing 2-step strategy for screening, based on selection of the individuals with potential CD by HLA-DQ typing and on longitudinal serologic CD screening in this selected group.