Coeliac disease and gastrointestinal symptom screening in adult first-degree relatives

The first-degree relatives (FDRs) of patients with coeliac disease are the main risk group for disease development. The study aims to evaluate the screening strategy in FDRs with negative coeliac serology based on human leukocyte antigen (HLA) genotyping, followed by duodenal biopsy, and to analyze the prevalence of gastrointestinal symptoms and the influence of gluten intake.

Adult FDRs with negative coeliac serology were invited to participate (n = 205), and a total of 139 completed the study protocol. HLA genotyping, transglutaminase antibody assessment, and duodenal biopsy were performed. Symptomatology was assessed using questionnaires during the various phases of dietary modification (baseline diet, gluten-free diet, and gluten overload).

The study included 139 participants (mean age, 42 years; 53.2% women). HLA-DQ2/8 was positive in 78.4% of the participants (homozygous, 15.1%; heterozygous, 63.3%). Histopathological alterations were noted in 37.1% of participants who underwent duodenal biopsy (Marsh I, 32.7%; Marsh IIIa, 4.4%). At baseline, symptoms were observed in 45.7% of the participants, and the proportion decreased to 24.5% after the gluten-free diet (P < 0.001). Symptoms were not associated with the presence of histological alterations or genetic risk. However, younger age (odds ratio [OR] = 0.91), female sex (OR = 2.9), and the presence of autoimmune disorders (OR = 2.8) were independently associated with a significant symptom response to the gluten-free diet.

Duodenal lymphocytosis and atrophy are frequently noted in FDRs, despite negative serological markers. In addition, gastrointestinal symptoms are commonly present and associated with gluten intake regardless of the histological pathology.