STRATEGY OF INDENTIFYING UNDETECTED COELIAC DISEASE IN FINNISH MULTIPLE CASE FAMILIES

Abstract

73 Family members of coeliac disease (CD) patients bear an increased risk for CD. The genetic susceptibility is mainly based on the HLA-DQ2 heterodimer. CD may be totally symptomless but it may still predispose the individuals for malignant diseases, osteopenia or infertility. Therefore specific and sensitive non-invasive screening methods are needed for case finding. Often a stepwise screening using gliadin antibodies as the first step is recommended. In this study we questioned the suggested strategy by testing the healthy family members of a large family material by gliadin and endomysial antibodies simultaneously. Retrospectively the sera were also tested for tissue transglutaminase antibodies (tTG) to evaluate the potential use of this observer non-dependent screening test in case finding of silent coeliac disease. We took advantage of a family material comprising 137 multiple case CD families. Altogether 788 family members joined (90%): 322 with previously diagnosed CD or DH, and 466 healthy family members. The healthy family members were first screened for endomysial (EMA) and gliadin antibodies (AGA) and small-bowel biopsies were performed on voluntary basis. Antibody positive healthy individuals and one CD patient of each family were analysed for HLA DQ2. Tissue transglutaminase (tTG) antibodies were tested using Quanta Lite™ tTG ELISA 708730 - Kit. Positive serology was found in 73 (15.7%) out of 466 healthy family members: 45 (9.7%) were positive for EMA and 28 (6.0%) for AGA only. Half of EMA positive individuals were negative for AGA. 43 (59%) antibody positive individuals underwent biopsy and 28 new untreated CD patients were found. 27 of 28 newly diagnosed CD patients were positive for EMA and one for AGA only. All but one of the probands and all new CD patients were positive for DQ2. 44 of 45 (98%) EMA positive family members carried the HLA DQ2. In contrast, only half (13/28) of the AGA positive persons were positive for HLA DQ2 (p<0.001). 58 (12.4%) tTG positive individuals were found, including all but 2 EMA positive individuals. 12/19 EMA negative but tTG positive persons were DQ2 positive. The correlation between tTG and EMA titres was good. Endomysial antibodies find considerably more silent coeliac disease patients among the healthy first-degree relatives of coeliac disease patients than gliadin antibodies. Thus EMA alone may be used as a first step screening for case finding. tTG antibody test correlates well with endomysial antibodies, but also finds additional individuals bearing the DQ alleles reported to be associated with CD. The total existence of CD among multiple case coeliac families (40% of all family members) is surprisingly high.