Serologic Markers in Screening for Coeliac Disease, Clinical significance and immunogenetic basis

University dissertation from Department of Medicine, University Hospital, SE-205 02 Malmö, Sweden

Abstract: The prevalence of coeliac disease (CD) was initially estimated to 1/1537. Based on serial analysis [GA and endomysial antibodies (EMA)], the prevalence was 6/1970 (0.30%). In autoimmune chronic hepatitis 5.4% and in IDDM 2.6% had CD, why regular screening for CD in these conditions seems motivated. The frequency of IgA-GA positivity was increased in alcoholic liver disease, PBC, primary sclerosing cholangitis, chronic hepatitis, and hepatitis C, as well as in IDDM, NIDDM, and in secondary diabetes to 11-24% compared with blood donors (5%). Consequently, investigation in GA-positive individuals with suspicion of CD should be completed with EMA/tTg. CD was correlated with HLA-DR3 and DQ2, whereas DQ1, DQ7, DR1, DR4 and DR5 were all inversely correlated. 79% of GA-positive but healthy individuals had DQ1, which would be expected to confer protection. The findings suggest GA-positivity to be independent of the HLA genotype in CD. From 848 IDDM patients 16 high titre GA patients were selected and compared with 37 matched low titre patients. Chronic thyroiditis, thyroid peroxidase and factor XIII IgA antibody positivity and HLA DRB1'13 were correlated with GA-positivity, while tissue transglutaminase IgG titres were inversely correlated. A tissue transglutaminase (tTg) ELISA method has been developed for CD-screening. The possibility to replace tTg by recombinant factor XIII was investigated. A patient with CD and antibodies against the active site of factor XIII is described. In sera from 20 patients with EMA and 20 controls no correlation between tTg and factor XIII was observed. Determination of antibody titres against factor XIII is not appropriate to use in screening for CD.

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