First-degree relatives and spouses of patients with celiac disease are at increased risk for autoimmune diseases, according to results of a study published online January 30 and in the July issue of Clinical Gastroenterology and Hepatology.

The risk of developing celiac disease is elevated among people who have first-degree relatives with the condition, but little is known about their risk for other autoimmune disorders. Genetics, environmental factors, and ascertainment bias may be at play.

Louise Emilsson, MD, PhD, from the Primary Care Research Unit, Vårdcentralen Värmlands Nysäter, Värmland County, Sweden, and the Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo in Norway, and colleagues conducted a population-based longitudinal cohort study to analyze the risk of developing Crohn's disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, or ulcerative colitis among the relatives and spouses of 29,096 individuals with celiac disease. The researchers used information on duodenal and jejunal biopsies (villus atrophy) collected from 1969 through 2008 in Sweden.

Each individual with celiac disease was matched with up to five control patients for sex, age, county, and year. Healthcare registries were used to identify all first-degree relatives and spouses of individuals with celiac disease and control patients. The study included 84,648 first-degree relatives and spouses of patients with celiac disease and 430,942 people associated with the control patients.

For all diseases considered, the incidence was higher among relatives and spouses of patients with celiac disease than among controls. During the period assessed (median, 10.8 years), 3333 first-degree relatives of patients with celiac disease (3.9%) and 12,860 first-degree relatives of controls (3.0%) developed a nonceliac autoimmune disease.

Genetic relatives and spouses of people with celiac disease had a similar risk of developing nonceliac autoimmune disorders. The HR for any nonceliac autoimmune disease in relatives of patients with celiac disease was 1.28 (95% CI, 1.23 - 1.33), and the HR in spouses of celiac patients was 1.20 (95% CI, 1.06 - 1.35). The risk of developing nonceliac autoimmune diseases was highest in the first 2 years after diagnosis of the index patients.

The fact that 4.3% of celiac relatives developed nonceliac autoimmune disease compared with 3.3% among relatives of the control group suggests a genetic component to autoimmune susceptibility, but the higher risk among spouses suggests an environmental component. The investigators suggest that the environmental finding might reflect a shared microbiome profile between spouses who eat the same foods.

Ascertainment bias might have arisen from the greater awareness of autoimmune diseases among relatives and spouses of patients with celiac disease, and perhaps by healthcare providers.

A limitation of the study is that the patient register consulted may not have included autoimmune diagnoses handled only in primary care, such as hypothyroidism and hyperthyroidism.

This study was funded by the Swedish Research Council. The authors have disclosed no relevant financial relationships.

Clin Gastroenterol Hepatol. 2015;13:1271-1277. Abstract