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High Prevalence of Celiac Disease Among Screened First-Degree Relatives



      To investigate the prevalence of first-degree relatives (FDRs) with celiac disease detected at screening and diagnostic significance of anti-tissue transglutaminase (anti-TTG).

      Patients and Methods

      We performed a retrospective cohort study of 104 patients with a diagnosis of celiac disease and their FDRs, collecting data from electronic records of Mayo Clinic and celiac disease registry from December 20, 1983, to May 22, 2017. We collected demographics, presenting symptoms, indication for testing, family history, number of other family members screened, biopsy reports, and results of serologic tests.


      Of 477 FDRs identified, 360 were screened (mean screening rate per family, 79%±25%) and 160 FDRs (44.4%) were diagnosed with celiac disease, at a mean age 31.9±21.6 years (62% female). All diagnosed FDRs had positive anti-TTG titers. Clinical features were documented in 148 diagnosed FDRs, of those 9 (6%) had classic, 97 (66%) had non-classic symptoms, and 42(28%) had no reported symptoms. Histology reports were available from 155 FDRs: 12 (8%) had Marsh 1, 77 (50%) had Marsh 3a, and 66 (43%) had Marsh 3b. A level of anti-TTG greater than or equal to 2.75 of the upper limit of normal identified FDRs with villous atrophy with 87% sensitivity, 82% specificity, and a positive predictive value of 95%.


      In a retrospective cohort study of patients diagnosed with celiac disease, we found a high prevalence of celiac disease among screened FDRs. High anti-TTG titers associated with villous atrophy on small bowel biopsies, irrespective of symptoms.

      Abbreviations and Acronyms:

      anti-TTG (anti–tissue transglutaminase), CD (celiac disease), EMA (endomysial antibodies immunoglobulin A), ESPGHAN (European Society for Pediatric Gastroenterology, Hepatology and Nutrition), FDR (first-degree relative), ICP (index case patient), IEL (intraepithelial lymphocyte), Ig (immunoglobulin), IQR (interquartile range), ROC (receiver operating characteristic), SBB (small bowel biopsy), ULN (upper limit of normal), VA (villous atrophy)
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        • Rubio-Tapia A.
        • Ludvigsson J.F.
        • Brantner T.L.
        • Murray J.A.
        • Everhart J.E.
        The prevalence of celiac disease in the United States.
        Am J Gastroenterol. 2012; 107 (quiz 1537, 1545): 1538-1544
        • Fasano A.
        Clinical presentation of celiac disease in the pediatric population.
        Gastroenterology. 2005; 128: S68-S73
        • Green P.H.R.
        The many faces of celiac disease: clinical presentation of celiac disease in the adult population.
        Gastroenterology. 2005; 128: S74-S78
        • Ludvigsson J.F.
        • Rubio-Tapia A.
        • van Dyke C.T.
        • et al.
        Increasing incidence of celiac disease in a North American population.
        Am J Gastroenterol. 2013; 108: 818-824
        • Almallouhi E.
        • King K.S.
        • Patel B.
        • et al.
        Increasing incidence and altered presentation in a population-based study of pediatric celiac disease in North America.
        J Pediatr Gastroenterol. 2017; 65: 432-437
        • Hill I.D.
        • Dirks M.H.
        • Liptak G.S.
        • et al.
        Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.
        J Pediatr Gastroenterol Nutr. 2005; 40: 1-19
        • Husby S.
        • Koletzko S.
        • Korponay-Szabo I.R.
        • et al.
        European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease.
        J Pediatr Gastroenterol Nutr. 2012; 54: 136-160
        • Lock R.J.
        • Pitcher M.C.
        • Unsworth D.J.
        IgA anti-tissue transglutaminase as a diagnostic marker of gluten sensitive enteropathy.
        J Clin Pathol. 1999; 52: 274-277
        • Klapp G.
        • Masip E.
        • Bolonio M.
        • et al.
        Celiac disease: the new proposed ESPGHAN diagnostic criteria do work well in a selected population.
        J Pediatr Gastroenterol Nutr. 2013; 56: 251-256
        • Mårild K.
        • Størdal K.
        • Hagman A.
        • Ludvigsson J.F.
        Turner syndrome and celiac disease: a case-control study.
        Pediatrics. 2016; 137: e20152232
        • Mazurek D.
        • Wyka J.
        Down syndrome—genetic and nutritional aspects of accompanying disorders.
        Rocz Panstw Zakl Hig. 2015; 66: 189-194
        • Canova C.
        • Pitter G.
        • Ludvigsson J.F.
        • et al.
        Celiac disease and risk of autoimmune disorders: a population-based matched birth cohort study.
        J Pediatr. 2016; 174: 146-152.e1
        • Mahmud F.H.
        • Murray J.A.
        • Kudva Y.C.
        • et al.
        Celiac disease in type 1 diabetes mellitus in a North American community: prevalence, serologic screening, and clinical features.
        Mayo Clin Proc. 2005; 80: 1429-1434
        • Rubio–Tapia A.
        • Van Dyke C.T.
        • Lahr B.D.
        • et al.
        Predictors of family risk for celiac disease: a population-based study.
        Clin Gastroenterol Hepatol. 2008; 6: 983-987
        • Hill I.D.
        • Fasano A.
        • Guandalini S.
        • et al.
        NASPGHAN clinical report on the diagnosis and treatment of gluten-related disorders.
        J Pediatr Gastroenterol Nutr. 2016; 63: 156-165
        • US Preventive Services Task Force
        • Bibbins-Domingo K.
        • Grossman D.C.
        • et al.
        Screening for Celiac disease: US Preventive Services Task Force recommendation statement.
        JAMA. 2017; 317: 1252-1257
        • Theethira T.G.
        • Dennis M.
        • Leffler D.A.
        Nutritional consequences of celiac disease and the gluten-free diet.
        Expert Rev Gastroenterol Hepatol. 2014; 8: 123-129
        • Rubio-Tapia A.
        • Kyle R.A.
        • Kaplan E.L.
        • et al.
        Increased prevalence and mortality in undiagnosed celiac disease.
        Gastroenterology. 2009; 137: 88-93
        • Farre C.
        • Humbert P.
        • Vilar P.
        • et al.
        Serological markers and HLA-DQ2 haplotype among first-degree relatives of celiac patients.
        Dig Dis Sci. 1999; 44: 2344-2349
        • Högberg L.
        • Fälth-Magnusson K.
        • Grodzinsky E.
        • Stenhammar L.
        Familial prevalence of coeliac disease: a twenty-year follow-up study.
        Scand J Gastroenterol. 2003; 38: 61-65
        • Bonamico M.
        • Ferri M.
        • Mariani P.
        • et al.
        Serologic and genetic markers of celiac disease: a sequential study in the screening of first degree relatives.
        J Pediatr Gastroenterol Nutr. 2006; 42: 150-154
        • Oberhuber G.
        • Granditsch G.
        • Vogelsang H.
        The histopathology of coeliac disease: time for a standardized report scheme for pathologists.
        Eur J Gastroenterol Hepatol. 1999; 11: 1185-1194
        • Hoffenberg E.J.
        • Bao F.
        • Eisenbarth G.S.
        • et al.
        Transglutaminase antibodies in children with a genetic risk for celiac disease.
        J Pediatr. 2000; 137: 356-360
        • Liu E.
        • Dong F.
        • Barón A.E.
        • et al.
        High Incidence of celiac disease in a long-term study of adolescents with susceptibility genotypes.
        Gastroenterology. 2017; 152: 1329-1336
        • Tommasini A.
        • Not T.
        • Kiren V.
        • et al.
        Mass screening for coeliac disease using antihuman transglutaminase antibody assay.
        Arch Dis Child. 2004; 89: 512-515
        • Hawamdeh H.
        • Al-Zoubi B.
        • Al Sharqi Y.
        • Qasrawi A.
        • Abdelaziz Y.
        • Barbar M.
        Association of tissue transglutaminase antibody titer with duodenal histological changes in children with celiac disease.
        Gastroenterol Res Pract. 2016; 2016 (erratum 2019;2019:2607194)
        • Troncone R.
        • Maurano F.
        • Rossi M.
        • et al.
        IgA antibodies to tissue transglutaminase: an effective diagnostic test for celiac disease.
        J Pediatr. 1999; 134: 166-171
        • Sulkanen S.
        • Halttunen T.
        • Laurila K.
        • et al.
        Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease.
        Gastroenterology. 1998; 115: 1322-1328
        • Hopper A.D.
        • Hadjivassiliou M.
        • Hurlstone D.P.
        • et al.
        What is the role of serologic testing in celiac disease? A prospective, biopsy-confirmed study with economic analysis.
        Clin Gastroenterol Hepatol. 2008; 6: 314-320
        • Trovato C.M.
        • Montuori M.
        • Anania C.
        • et al.
        Are ESPGHAN “biopsy-sparing” guidelines for celiac disease also suitable for asymptomatic patients?.
        Am J Gastroenterol. 2015; 110: 1485-1489