A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways

BMC Medicine

Julie A Pasco⁵  Matthew A Brown⁸  Ban-Hock Toh²  Geoffrey C Nicholson⁴  Wendy Pollock²  Ross E Knight¹  Mark A Kotowicz⁵  Jason A Tye-Din⁷  Kathryn Addison⁸  Marylia J Costa³  Patrick Danoy⁸  Emma L Duncan⁴  Roberta Taylor²  Margaret J Henry⁶  Robert P Anderson⁹ 

[1] Geelong Gastroenterology, Level 1, 83 Myers St, Geelong, Victoria 3220, Australia;Healthscope Pathology, Melbourne, Victoria, Australia;Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia;Endocrinology, Royal Brisbane and Women’s Hospital, Butterfield Rd, Herston, QLD 4029, Australia;NorthWest Academic Centre, Department of Medicine, The University of Melbourne, St Albans, Victoria, Australia;School of Medicine, Deakin University, Geelong, Victoria, Australia;Department of Gastroenterology, The Royal Melbourne Hospital, Melbourne Health, Grattan St, Parkville, Victoria 3050, Australia;Human Genetics Group, University of Queensland Diamantina Institute, Level 5, Translational Research Institute, 37 Kent St, Woolloongabba, QLD 4102, Australia;Current address: ImmusanT, Inc., ImmusanT Inc., One Kendall Square, Building 200, LL, Suite 4, Cambridge, MA 02139, USA

关键词: Prevalence;    Immunogenetics;    Deamidated gliadin peptide;    Transglutaminase;    Serology;    Epidemiology;    Diagnosis;    Celiac disease;   

Others  :  855740
DOI  :  10.1186/1741-7015-11-188

 received in 2013-05-08, accepted in 2013-08-02,  发布年份 2013

【 摘 要 】

Background

Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach.

Methods

The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with ‘biopsy-confirmed’ CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology.

Results

Only five ‘biopsy-confirmed’ patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively.

Conclusions

Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies.

【 授权许可】

   
2013 Anderson et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Walker MM, Murray JA, Ronkainen J, Aro P, Storskrubb T, D’Amato M, Lahr B, Talley NJ, Agreus L: Detection of celiac disease and lymphocytic enteropathy by parallel serology and histopathology in a population-based study. Gastroenterology 2010, 139:112-119.
• [2]Biagi F, Klersy C, Balduzzi D, Corazza GR: Are we not over-estimating the prevalence of coeliac disease in the general population? Ann Med 2010, 42:557-561.
• [3]Walker-Smith J, Guandalini S, Schmitz J, Shmerling D, Visakorpi J: Revised criteria for diagnosis of coeliac disease. Report of working group of European society of paediatric gastroenterology and nutrition. Arch Dis Child 1990, 65:909-911.
• [4]Husby S, Koletzko S, Korponay-Szabo IR, Mearin ML, Phillips A, Shamir R, Troncone R, Giersiepen K, Branski D, Catassi C, 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.
• [5]National Institute for Health and Clinicial Excellence: NICE Guidelines. 2009. http://www.nice.org.uk/CG86 webcite
• [6]Kurppa K, Collin P, Viljamaa M, Haimila K, Saavalainen P, Partanen J, Laurila K, Huhtala H, Paasikivi K, Maki M, et al.: Diagnosing mild enteropathy celiac disease: a randomized, controlled clinical study. Gastroenterology 2009, 136:816-823.
• [7]Hopper AD, Hadjivassiliou M, Hurlstone DP, Lobo AJ, McAlindon ME, Egner W, Wild G, Sanders DS: 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.
• [8]Hopper AD, Cross SS, Hurlstone DP, McAlindon ME, Lobo AJ, Hadjivassiliou M, Sloan ME, Dixon S, Sanders DS: Pre-endoscopy serological testing for coeliac disease: evaluation of a clinical decision tool. BMJ 2007, 334:729.
• [9]Maki M, Mustalahti K, Kokkonen J, Kulmala P, Haapalahti M, Karttunen T, Ilonen J, Laurila K, Dahlbom I, Hansson T, et al.: Prevalence of Celiac disease among children in Finland. N Engl J Med 2003, 348:2517-2524.
• [10]Kurppa K, Ashorn M, Iltanen S, Koskinen LL, Saavalainen P, Koskinen O, Maki M, Kaukinen K: Celiac disease without villous atrophy in children: a prospective study. J Pediatr 2010, 157:373-380.
• [11]Chin MW, Mallon DF, Cullen DJ, Olynyk JK, Mollison LC, Pearce CB: Screening for coeliac disease using anti-tissue transglutaminase antibody assays, and prevalence of the disease in an Australian community. Med J Aust 2009, 190:429-432.
• [12]Hovell CJ, Collett JA, Vautier G, Cheng AJ, Sutanto E, Mallon DF, Olynyk JK, Cullen DJ: High prevalence of coeliac disease in a population-based study from western Australia: a case for screening? Med J Aust 2001, 175:247-250.
• [13]Henderson KN, Tye-Din JA, Reid HH, Chen Z, Borg NA, Beissbarth T, Tatham A, Mannering SI, Purcell AW, Dudek NL, et al.: A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease. Immunity 2007, 27:23-34.
• [14]Karell K, Louka AS, Moodie SJ, Ascher H, Clot F, Greco L, Ciclitira PJ, Sollid LM, Partanen J, European Genetics Cluster on Celiac D: HLA types in celiac disease patients not carrying the DQA1*05-DQB1*02 (DQ2) heterodimer: results from the European Genetics Cluster on Celiac Disease. Hum Immunol 2003, 64:469-477.
• [15]Lundin KE, Scott H, Fausa O, Thorsby E, Sollid LM: T cells from the small intestinal mucosa of a DR4, DQ7/DR4, DQ8 celiac disease patient preferentially recognize gliadin when presented by DQ8. Hum Immunol 1994, 41:285-291.
• [16]Lundin KE, Scott H, Hansen T, Paulsen G, Halstensen TS, Fausa O, Thorsby E, Sollid LM: Gliadin-specific, HLA-DQ(alpha 1*0501, beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients. J Exp Med 1993, 178:187-196.
• [17]Tye-Din JA, Stewart JA, Dromey JA, Beissbarth T, van Heel DA, Tatham A, Henderson K, Mannering SI, Gianfrani C, Jewell DP, et al.: Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. Sci Transl Med 2010, 2:41ra51.
• [18]Pasco JA, Nicholson GC, Kotowicz MA: Cohort profile: Geelong osteoporosis study. Int J Epidemiol 2012, 41:1565-1575.
• [19]Henry MJ, Pasco JA, Nicholson GC, Seeman E, Kotowicz MA: Prevalence of osteoporosis in Australian women: Geelong Osteoporosis Study. J Clin Densitom 2000, 3:261-268.
• [20]Koskinen L, Romanos J, Kaukinen K, Mustalahti K, Korponay-Szabo I, Barisani D, Bardella MT, Ziberna F, Vatta S, Szeles G, et al.: Cost-effective HLA typing with tagging SNPs predicts celiac disease risk haplotypes in the Finnish, Hungarian, and Italian populations. Immunogenetics 2009, 61:247-256.
• [21]Monsuur AJ, de Bakker PI, Zhernakova A, Pinto D, Verduijn W, Romanos J, Auricchio R, Lopez A, van Heel DA, Crusius JB, et al.: Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms. PLoS ONE 2008, 3:e2270.
• [22]Mullighan CG, Bunce M, Welsh KI: High-resolution HLA-DQB1 typing using the polymerase chain reaction and sequence-specific primers. Tissue Antigens 1997, 50:688-692.
• [23]Bunce M, O’Neill CM, Barnardo MC, Krausa P, Browning MJ, Morris PJ, Welsh KI: Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP). Tissue Antigens 1995, 46:355-367.
• [24]Olerup O, Aldener A, Fogdell A: HLA-DQB1 and -DQA1 typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours. Tissue Antigens 1993, 41:119-134.
• [25]Arguelles-Grande C, Tennyson CA, Lewis SK, Green PH, Bhagat G: Variability in small bowel histopathology reporting between different pathology practice settings: impact on the diagnosis of coeliac disease. J Clin Pathol 2012, 65:242-247.
• [26]Collin P, Kaukinen K, Vogelsang H, Korponay-Szabo I, Sommer R, Schreier E, Volta U, Granito A, Veronesi L, Mascart F, et al.: Antiendomysial and antihuman recombinant tissue transglutaminase antibodies in the diagnosis of coeliac disease: a biopsy-proven European multicentre study. Eur J Gastroenterol Hepatol 2005, 17:85-91.
• [27]Wahnschaffe U, Ullrich R, Riecken EO, Schulzke JD: Celiac disease-like abnormalities in a subgroup of patients with irritable bowel syndrome. Gastroenterology 2001, 121:1329-1338.
• [28]Sugai E, Hwang HJ, Vazquez H, Smecuol E, Niveloni S, Mazure R, Maurino E, Aeschlimann P, Binder W, Aeschlimann D, et al.: New serology assays can detect gluten sensitivity among enteropathy patients seronegative for anti-tissue transglutaminase. Clin Chem 2010, 56:661-665.
• [29]Catassi C, Ratsch IM, Fabiani E, Rossini M, Bordicchia F, Candela F, Coppa GV, Giorgi PL: Coeliac disease in the year 2000: exploring the iceberg. Lancet 1994, 343:200-203.
• [30]Tosco A, Salvati VM, Auricchio R, Maglio M, Borrelli M, Coruzzo A, Paparo F, Boffardi M, Esposito A, D’Adamo G, et al.: Natural history of potential celiac disease in children. Clin Gastroenterol Hepatol 2011, 9:320-325.
• [31]Sperandeo MP, Tosco A, Izzo V, Tucci F, Troncone R, Auricchio R, Romanos J, Trynka G, Auricchio S, Jabri B, et al.: Potential celiac patients: a model of celiac disease pathogenesis. PLoS ONE 2011, 6:e21281.
• [32]Troncone R, Greco L, Mayer M, Paparo F, Caputo N, Micillo M, Mugione P, Auricchio S: Latent and potential coeliac disease. Acta Paediatr Suppl 1996, 412:10-14.
• [33]Schwertz E, Kahlenberg F, Sack U, Richter T, Stern M, Conrad K, Zimmer KP, Mothes T: Serologic assay based on gliadin-related nonapeptides as a highly sensitive and specific diagnostic aid in celiac disease. Clin Chem 2004, 50:2370-2375.
• [34]Kaukinen K, Partanen J, Maki M, Collin P: HLA-DQ typing in the diagnosis of celiac disease. Am J Gastroenterol 2002, 97:695-699.
• [35]Dieterich W, Laag E, Schopper H, Volta U, Ferguson A, Gillett H, Riecken EO, Schuppan D: Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology 1998, 115:1317-1321.
• [36]Hadithi M, von Blomberg BM, Crusius JB, Bloemena E, Kostense PJ, Meijer JW, Mulder CJ, Stehouwer CD, Pena AS: Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease. Ann Intern Med 2007, 147:294-302.
• [37]Rubio-Tapia A, Van Dyke CT, Lahr BD, Zinsmeister AR, El-Youssef M, Moore SB, Bowman M, Burgart LJ, Melton LJ 3rd, Murray JA: Predictors of family risk for celiac disease: a population-based study. Clin Gastroenterol Hepatol 2008, 6:983-987.
• [38]Doolan A, Donaghue K, Fairchild J, Wong M, Williams AJ: Use of HLA typing in diagnosing celiac disease in patients with type 1 diabetes. Diabetes Care 2005, 28:806-809.