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Åke Lernmark

Principal investigator

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Searching for Celiac Disease Screening-detected celiac disease in an HLA-genotyped birth cohort

Author

  • Sara Björck

Summary, in English

Objectives: Celiac disease is a common immune mediated enteropathy strongly associated with HLA-DQB1*02 (DQ2), *0302 (DQ8), or both and the presence of tissue transglutaminase autoantibodies (tTGA). Prevalence studies have revealed that most affected individuals go undetected because of subclinical signs or being asymptomatic rendering screening a method for identification. However, less is known about subclinical manifestations of screening-detected celiac disease during childhood and if these motivate identification and treatment. The overall aim of the present research was to identify children with screening-detected celiac disease in an HLA-genotyped birth cohort and to study systemic cytokines and bone mineral density (BMD) in these children.

Methods: Children were HLA-genotyped at birth and offered screening at three and nine years of age by detection of tTGA in plasma using radioligand binding assays. Children repeatedly positive for tTGA underwent intestinal biopsy to confirm diagnosis of celiac disease. The cytokines IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13, and TNF-α were analysed at time of diagnosis and after treatment with a gluten-free diet and compared with matched controls. At nine years of age, children with screening-detected celiac disease were examined by dual X-ray absorptiometry for analysis of BMD and for serum 25(OH) vitamin D3 and plasma parathyroid hormone (PTH) and compared to matched controls.

Results: Screening-detected celiac disease was found in 3.5% (56/1618) of three year old children having HLA-risk alleles compared with none (0/1815) among children not having these risk alleles (p<0.001). A follow-up screening at nine years of age identified an additional 3.8% (72/1907) with celiac disease in the HLA-risk group compared with none (0/2167) in the control group (p<0.001). Three-year old children with screening-detected celiac disease had systemically elevated pro-inflammatory cytokines of both TH1 and TH2 pattern compared to controls of which most were down-regulated after starting a gluten-free diet. At nine years of age, children with screening-detected celiac disease had lower BMD, lower levels of vitamin D but higher PTH levels compared with matched controls. In contrast, children on a gluten-free diet did not differ from their matched controls.

Conclusions: Screening-detected celiac disease is only found among children at genetic risk but repeated testing during childhood is necessary to detect new patients. HLA-genotyping could therefore be used to select large populations to be screened for celiac disease. Children with screening-detected celiac disease have systemically elevated pro-inflammatory cytokines and low BMD but normal values on a gluten-free diet, indicating that children with screening-detected celiac disease could benefit from early identification and treatment.

Department/s

  • Diabetes and Celiac Unit
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2015

Language

English

Publication/Series

Lund University Faculty of Medicine Doctoral Dissertation Series

Volume

2015:106

Document type

Dissertation

Publisher

Diabetes and Celiac Disease Unit

Topic

  • Pediatrics

Keywords

  • bone mineral density
  • inflammation
  • cytokine
  • screening
  • HLA
  • tissue transglutaminase antibody
  • children
  • Celiac disease
  • vitamin D
  • parathyroid hormone

Status

Published

Research group

  • Diabetes and Celiac Unit

Supervisor

  • Daniel Agardh
  • Åke Lernmark

ISBN/ISSN/Other

  • ISSN: 1652-8220
  • ISBN: 978-91-7619-185-9

Defence date

23 October 2015

Defence time

09:00

Defence place

CRC Aula (CRC93-10-002) Clinical Research Center, Jan Waldenströms gata 35, Malmö

Opponent

  • Katri Kaukinen (Professor)