United European Gastroenterol J. 2022 Jul;10(6):585-593. doi: 10.1002/ueg2.12255.Epub 2022 May 25.

Saana Paavola ^1 2, Kalle Kurppa ^1 3 4, Heini Huhtala ⁵, Päivi Saavalainen ⁶, Katri Lindfors ¹, Katri Kaukinen ^1 2

Author information

¹Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

²Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.

³Tampere Center for Child, Adolescent and Maternal Health Research, Tampere University and Tampere University Hospital, Tampere, Finland.

⁴The University Consortium of Seinäjoki and Seinäjoki Central Hospital, Seinäjoki, Finland.

⁵Faculty of Social Sciences, Tampere University, Tampere, Finland.

⁶Research Programs Unit, Immunobiology, and Department of Medical Genetics, University of Helsinki, Helsinki, Finland.

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.