Autoantibodies and Histogenesis of Celiac Disease

Kamran Rostami1, Chris J.J. Mulder2, Steven Stapel5, B. Mary E. von Blomberg3, Jo Kerckhaert6, Jos W.R. Meijer7, Salvador A. Pena4, Hugo S.A. Heymans8

1)Department of Gastroenterology Withybush General Hospital, Pembrokeshire, Haverfordwest, UK, 2) Department of Gastroenterology, 3) Pathology and 4) Gastrointestinal Immunogenetic Free University Amsterdam, 5) Central Laboratory of Blood Transfusion (CLB) Amsterdam, 6) Department of Immunology and 7) Pathology Rijnstate Hospital Arnhem, 8) Emm’a Children Hospital AMC, University of Amsterdam, The Netherlands

Abstract

Objective. Autoantibodies are used as markers for celiac disease (CD) identifying patients with mucosal lesions. The purpose of this study was to evaluate the sensitivity and role of the autoantibodies such as IgA antiendomysium (EMA), IgA antigliadin (AGA) and the IgA antitissue transglutaminase (tTGA) in histogenesis of celiac disease.

Methods. Seventy-nine cases including 30 untreated celiacs, 5 celiacs on gluten-free diet (GFD), 41 first degree relatives and 3 non-relatives suspected for CD were investigated. Three untreated celiacs with IgA deficiency were excluded from this study group. IgA antibodies to tTGA were determined by ELISA, as described before. Twelve of 41 relatives and 2 cases of non relatives suspected with positive serology underwent a small intestinal biopsy. Results were correlated with the degrees of abnormality of the intestinal mucosa in patients with CD. Intestinal biopsies obtained from study population were evaluated for histological quantification.

Results. Celiacs and suspected cases with positive EMA/AGA and or tTGA showed shorter villi (p < 0.007) and/or a higher number of intraepithelial lymphocytes (IEL) (p < 0.035). The sensitivity of serology (EMA, AGA, tTGA) in patients with Marsh IIIc was 100%. However, in patients with Marsh IIIa the sensitivity for EMA, AGA, and tTGA was 40%, 50% and 20% respectively.

Conclusions. The appearance of antibodies is related to the degree of mucosal infiltration by IELs. Although tTGA, like EMA provide a highly sensitive parameter for the detection of celiacs with severe mucosal damage, it appears to be less sensitive (even less than AGA) in celiac patients with milder histopathological abnormalities. However, it should be recognized that the substantial part of the celiac population present with these milder forms of mucosal abnormalities. Using tTGA as a single test in screening may result in missing up to 60-70% of celiacs with mild mucosal abnormalities. Combination with other screening tests (at least with AGA) is essential and strongly recommended.

Key words

Celiac disease – autoantibodies – gluten-free diet – intraepithelial lymphocytes – villous atrophy