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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 comp

Aims/hypothesisThe aim of our study was to test the hypothesis that HLA genotypes conferring risk of diabetes, cord blood autoantibodies, or both are associated with increased birthweight. Methods: HLA genotypes were determined in dried blood spots of cord blood from a total of 16,709 children born to healthy mothers in the Diabetes Prediction in Skane (DiPiS) study, a population-based observational clinical investigation of newborn children. Children born to mothers with diabetes or gestational diabetes were excluded. Autoantibodies to glutamic acid decarboxylase (GAD65Ab) and insulinoma-associated protein 2 were determined in standard radioligand binding assays. Birthweight was adjusted for gestational age and divided into quartiles. The upper quartile was defined as high relative birthweight (HrBW) and the lower quartile as low relative birthweight (LrBW). Results: Genotypes conferring risk of type 1 diabetes were strongly associated with relative birthweight (rBW) (p=0.01). The high-risk HLA-DQ2/8, DQ8/0604 and DQ8/X genotypes were associated with HrBW (odds ratio [OR] [95% CI]=1.20 [1.08-1.33], p=0.0006). The HLA-DQB1*0603 allele, which is negatively associated with type 1 diabetes, was also associated with HrBW (p=0.025), confirming a previous report on DQB1*0603-linked HLA-DR13. GAD65Ab were negatively associated with HrBW (OR [95% CI]=0.72 [0.56-0.93], p=0.01). Regression analysis showed that the HLA-associated increase in rBW was independent of confounding factors. Conclusions/Interpreation: HLA genotypes may be associated with intrauterine growth independent of type 1 diabetes risk. The epidemiological observation that high birthweight is a risk factor for type 1 diabetes could possibly result from a moderating effect on intrauterine growth of HLA genotypes conferring a high risk of diabetes.