Long-term Consequences of Undiagnosed Celiac Seropositivity

• Published in: The American journal of gastroenterology Vol. 115; no. 10; pp. 1681 - 1688
• Main Authors: Kårhus, Line Lund, Skaaby, Tea, Petersen, Janne, Madsen, Anja Lykke, Thuesen, Betina Heinsbæk, Schwarz, Peter, Rumessen, Jüri J., Linneberg, Allan
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer 01.10.2020; Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subjects: Adolescent; Adult; Aged; Antibodies; Antibodies - immunology; Asymptomatic; Autoantibodies - immunology; Autoimmune diseases; Biobanks; Biological Specimen Banks; Biomarkers; Biopsy; Breast cancer; Breast Neoplasms - epidemiology; Cancer; Cardiovascular disease; Cardiovascular Diseases - epidemiology; Celiac disease; Celiac Disease - epidemiology; Celiac Disease - immunology; Denmark - epidemiology; Emigration; Female; Gastroenterology; Gastrointestinal Neoplasms - epidemiology; Gliadin - immunology; Gluten; GTP-Binding Proteins - immunology; Head & neck cancer; Head and Neck Neoplasms - epidemiology; Humans; Immunoglobulin A - immunology; Immunoglobulin G - immunology; Immunoglobulins; Incidence; Lymphoma; Male; Middle Aged; Mortality; Neoplasms - epidemiology; Peptides; Population; Prevalence; Proportional Hazards Models; Risk Factors; Transglutaminases - immunology; Undiagnosed Diseases - epidemiology; Uterine cancer; Uterine Neoplasms - epidemiology; Young Adult; Denmark
• ISSN: 0002-9270; 1572-0241; 1572-0241
• DOI: 10.14309/ajg.0000000000000737

Diagnosed celiac disease (CD) is associated with lymphoproliferative malignancy and gastrointestinal cancer, but little is known about the long-term consequences of undiagnosed CD. We aimed to investigate long-term consequences of undiagnosed CD for mortality and incidence of cancer and other chronic diseases. We screened biobank serum samples for immunoglobulin (Ig) A and IgG tissue transglutaminase (TTG) and IgG deamidated gliadin peptide in a study of 8 population-based cohort studies comprising 16,776 participants examined during 1976-2012 and followed with >99% complete follow-up in Danish nationwide registries until December 31, 2017, regarding vital status and incidence of diseases. Undiagnosed CD was defined as antibody positivity (IgA-TTG or IgG-TTG ≥ 7 U/mL and/or IgG deamidated gliadin peptide ≥ 10 U/mL) in individuals without a diagnosis of CD recorded in the National Patient Register. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox regression analyses with age as the underlying time scale. The prevalence of undiagnosed CD was 1.0% with no statistically significant increase over time. Undiagnosed CD was associated with increased risk of cancer overall (HR, 1.57; 95% CI, 1.16-2.11), gastrointestinal cancer (HR, 2.33; 95% CI, 1.35-4.04), cancer of the uterus (HR, 3.95; 95% CI, 1.46-10.69), breast cancer (HR, 1.98; 95% CI, 1.02-3.82), head and neck cancer (HR, 3.12; 95% CI, 1.15-8.43), and cardiovascular disease (HR, 1.37; 95% CI, 1.01-1.85). We found no statistically significant association between undiagnosed CD and mortality (HR, 1.19; 95% CI, 0.87-1.61). Undiagnosed CD was associated with increased risk of cardiovascular disease and cancer suggesting that untreated CD has serious long-term health consequences not only affecting the gastrointestinal tract (see Visual Abstract, Supplementary Digital Content, http://links.lww.com/AJG/B566).