LAUSR

Abstract Background Serological screening of the relatives of coeliac disease patients is widely endorsed. However, the need for and the optimal timing of possible re‐testing of once seronegative at‐risk individuals for coeliac disease remain unclear. Objective We investigated this issue by inviting a large cohort of previously screening‐negative relatives of patients with coeliac disease to participate in a follow‐up study. Methods Altogether 599 relatives of coeliac disease index patients not diagnosed with coeliac disease in a screening study carried out in 2006–2010 were asked about possible later diagnosis or re‐tested with coeliac disease autoantibodies in 2017–2021. Besides incidence, the possible impact of various patient‐related clinical factors and HLA haplotype on the later diagnosis or screening positivity was examined. Results Fifteen (2.5%) relatives were either diagnosed with a coeliac disease (n = 8) during the follow‐up period or were found to be screening‐positive in the re‐testing (n = 7), giving a combined annual incidence of 221/100,000 person‐years in all relatives and 336/100,000 among those carrying coeliac disease‐associated HLA DQ2/DQ8. The new cases more often carried the high‐risk (DQ2.5/2.5 or DQ2.5/2.2; 35.7% vs. 7.4%, respectively, p < 0.001) HLA and were younger at initial screening (23.3 vs. 40.5 years, p = 0.028) and – in spite of a negative screening outcome – had higher median transglutaminase antibody level in the first study than those not affected. There were no significant differences between the affected and non‐affected relatives in other demographic data, degree of kinship with the index, current symptoms or frequency of chronic co‐morbidities. Conclusion The incidence rate for later coeliac disease diagnosis or new seropositivity in relatives who had been tested once was 221/100,000 person‐years in all and 336/100,000 among those carrying at‐risk HLA genetics after ∼10 years of follow‐up. HLA‐typing could help to target a subgroup of relatives who would benefit most from re‐testing.