Aspects of immunogenetics, infections, and nutrition on the risk of celiac disease autoimmunity in an Ethiopian pediatric birth cohort
Författare
Summary, in English
Background: Celiac disease (CD) is an immune-mediated inflammatory disease of the intestine in genetically susceptible individuals caused by loss of tolerance to the storage proteins (gluten) in wheat, rye, and barley. Little is known about CD and associated risk factors in Sub-Saharan African countries including Ethiopia. The main aim of the present thesis was to explore how the incidence of celiac disease autoimmunity (CDA) associates with genetic and environmental factors with emphasis on the diet and infections in an Ethiopian pediatric population.
Methods: Data from the general population were used for longitudinally prospective and retrospective studies. Serum samples collected from women and kept in a repository were examined for tissue transglutaminase autoantibodies (tTGA) using radioligand binding assays (RBA). Children from a birth cohort were prospectively followed for CDA and evaluated for genetic risk factors (HLA-DQ). Screening for CDA was performed annually from age 2 years by an ELISA. Children with positive tTGA results were retested using RBA and if persistently confirmed as tTGA positive, they were defined as having CDA. Parents were interviewed to obtain information on diet and infections of the study participants. An integrated cohort provided information on maternal tuberculosis exposure. At the age of 4 years, serum samples from children were tested for serum Helicobacter pylori (HP) antibodies using an ELISA.
Results: The prevalence of CDA ranged from 0.05% to 0.6% (1:2000 to 1:174). Children are more likely than adults to have CDA. There were no differences among the gender of the birth cohort. The distribution of the CD associated HLA risk-haplotypes, HLA-DQ2, and -DQ8, were comparable to that of the Swedish population. CDA was not associated with either Ethiopian traditional diet or Mycobacterium tuberculosis and Helicobacter pylori infections.
Conclusions: Although prevalence of CDA in Ethiopian children had increased more than tenfold compared to a screened adult female population, it was still lower than the pooled global prevalence. Despite the differences in individual HLA-DQ2 and HLA-DQ8 predisposing risk-haplotypes for CD that were found between the Ethiopian and Swedish cohort, the distribution of CD risk-genotypes was overall the same. Neither was the frequency of consumption of cereals based on teff nor wheat among study participants associated with CDA. Moreover, neither latent Mycobacterium tuberculosis exposure nor H. pylori infections were associated with the incidence of CDA.
Methods: Data from the general population were used for longitudinally prospective and retrospective studies. Serum samples collected from women and kept in a repository were examined for tissue transglutaminase autoantibodies (tTGA) using radioligand binding assays (RBA). Children from a birth cohort were prospectively followed for CDA and evaluated for genetic risk factors (HLA-DQ). Screening for CDA was performed annually from age 2 years by an ELISA. Children with positive tTGA results were retested using RBA and if persistently confirmed as tTGA positive, they were defined as having CDA. Parents were interviewed to obtain information on diet and infections of the study participants. An integrated cohort provided information on maternal tuberculosis exposure. At the age of 4 years, serum samples from children were tested for serum Helicobacter pylori (HP) antibodies using an ELISA.
Results: The prevalence of CDA ranged from 0.05% to 0.6% (1:2000 to 1:174). Children are more likely than adults to have CDA. There were no differences among the gender of the birth cohort. The distribution of the CD associated HLA risk-haplotypes, HLA-DQ2, and -DQ8, were comparable to that of the Swedish population. CDA was not associated with either Ethiopian traditional diet or Mycobacterium tuberculosis and Helicobacter pylori infections.
Conclusions: Although prevalence of CDA in Ethiopian children had increased more than tenfold compared to a screened adult female population, it was still lower than the pooled global prevalence. Despite the differences in individual HLA-DQ2 and HLA-DQ8 predisposing risk-haplotypes for CD that were found between the Ethiopian and Swedish cohort, the distribution of CD risk-genotypes was overall the same. Neither was the frequency of consumption of cereals based on teff nor wheat among study participants associated with CDA. Moreover, neither latent Mycobacterium tuberculosis exposure nor H. pylori infections were associated with the incidence of CDA.
Publiceringsår
2023
Språk
Engelska
Publikation/Tidskrift/Serie
Lund University, Faculty of Medicine Doctoral Dissertation Series
Issue
2023:12
Fulltext
- Available as PDF - 17 MB
- Download statistics
Dokumenttyp
Doktorsavhandling
Förlag
Lund University, Faculty of Medicine
Ämne
- Immunology in the medical area
Nyckelord
- celiac disease
- HLA-DQ2
- HLA-DQ8
- infection
- diet
Status
Published
Forskningsgrupp
- Celiac Disease and Diabetes Unit
Handledare
- Daniel Agardh
- Carin Andrén Aronsson
- Taye Tolera Balcha
- Åsa Håkansson
ISBN/ISSN/Övrigt
- ISSN: 1652-8220
- ISBN: 978-91-8021-351-6
Försvarsdatum
10 februari 2023
Försvarstid
09:00
Försvarsplats
Medelhavet, Inga Marie Nilssons gata 53, ingång 46, Skånes Universitetssjukhus i Malmö
Opponent
- Govind Makharia (Professor)