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Autoimmune Disease in First-Degree Relatives and Spouses of Individuals With Celiac Disease

  • Louise Emilsson
    Correspondence
    Reprint requests Address requests for reprints to: Louise Emilsson, MD, PhD, Vårdcentralen Värmlands Nysäter, Nyströms väg 5, 66195 Värmlands Nysäter, Sweden. fax: (46) (0) 533-30214.
    Affiliations
    Primary Care Research Unit, Vårdcentralen Värmlands Nysäter, Värmland County, Sweden

    Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Oslo, Norway
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  • Cisca Wijmenga
    Affiliations
    Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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  • Joseph A. Murray
    Affiliations
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
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  • Jonas F. Ludvigsson
    Affiliations
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
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Published:January 30, 2015DOI:https://doi.org/10.1016/j.cgh.2015.01.026

      Background & Aims

      First-degree relatives of individuals with celiac disease are at increased risk for this disorder, but little is known about their risk for other autoimmune diseases. We assessed the risk of nonceliac autoimmune disease in first-degree relatives and spouses of people with celiac disease.

      Methods

      We identified individuals with celiac disease by searching computerized duodenal and jejunal biopsies, collected from 1969 through 2008, at 28 pathology departments in Sweden. Celiac disease was identified based on biopsy reports of villous atrophy (equal to Marsh grade 3; n = 29,096). Individuals with celiac disease were matched with up to 5 controls (people without celiac disease) for sex, age, county, and calendar year (total, 144,522 controls). Through Swedish health care registries, we identified all first-degree relatives (fathers, mothers, siblings, and offspring) and spouses of individuals with celiac disease (n = 84,648) and controls (n = 430,942). We used Cox regression analysis to calculate hazard ratios (HRs) for nonceliac autoimmune disease (Crohn’s disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, or ulcerative colitis) in these groups.

      Results

      During the follow-up period (median, 10.8 y), 3333 of the first-degree relatives of patients with celiac disease (3.9%) and 12,860 relatives of controls (3.0%) had an autoimmune disease other than celiac disease. First-degree relatives of people with celiac disease were at increased risk of nonceliac autoimmune disease, compared with controls (HR, 1.28; 95% confidence interval, 1.23–1.33), as were spouses (HR, 1.20; 95% confidence interval, 1.06–1.35). Risk estimates for nonceliac autoimmune disease did not differ between first-degree relatives and spouses of individuals with celiac disease (interaction test: P = .11). HRs for nonceliac autoimmune disease were highest in the first 2 years of follow-up evaluation.

      Conclusions

      First-degree relatives and spouses of individuals with celiac disease are at increased risk of nonceliac autoimmune disease. In addition to genetic factors, environmental factors and ascertainment bias might contribute to the increased risk of autoimmunity in first-degree relatives of individuals with celiac disease.

      Keywords

      Abbreviations used in this paper:

      CD (celiac disease), CI (confidence interval), FDR (first-degree relative), HR (hazard ratio), RA (rheumatoid arthritis), SLE (systemic lupus erythematosus), T1DM (type I diabetes mellitus), UC (ulcerative colitis)
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