eISSN: 1897-4317
ISSN: 1895-5770
Gastroenterology Review/Przegląd Gastroenterologiczny
Bieżący numer Archiwum Artykuły zaakceptowane O czasopiśmie Bazy indeksacyjne Prenumerata Kontakt Zasady publikacji prac
Portal dla gastroenterologów!
SCImago Journal & Country Rank
Poleć ten artykuł:
Artykuł oryginalny

The prevalence of celiac disease in patients with irritable bowel syndrome and its subtypes

Danuta Domżał-Magrowska, Marek K. Kowalski, Piotr Szcześniak, Magdalena Bulska, Daria Orszulak-Michalak, Ewa Małecka-Panas

Plik artykułu:
- the prevalence.pdf  [0.10 MB]


Irritable bowel syndrome (IBS) is a chronic condition with variable gastrointestinal symptoms in the absence of organic abnormalities. It is characterised by chronic or recurrent abdominal pain or discomfort, bloating, and alternation of bowel habits. There are three sub- types of IBS: with predominating diarrhoea (IBS-D), constipation (IBS-C), or mixed (IBS-M). Diagnosis of IBS is based on symptom assessment: the Rome III criteria [1]. In patients over 50 years old and with alarm symptoms, colonoscopy is performed.
One of the diseases that shares some symptoms with IBS is celiac disease (CD), which is an immune-mediated small bowel enteropathy, caused by a permanent intolerance to gluten. It occurs in genetically predisposed individuals with specific histocompatibility antigens. In the course of CD, gliadin (one of the proteins belonging to the gluten) is treated with tissue transglutaminase II, which catalyses its deamidation. Deamidated gliadin peptides are more immunogenic than gliadin and bind with the human leukocyte antigen HLA-DQ2 or DQ8 receptors on antigen-presenting cells. As the next step, some gliadin epitopes are presented to Th1 lymphocytes, which in turn stimulate B cells to generate specific antibodies against tissue transglutaminase II (anti-tTG), gliadin, and deamidated gliadin peptides (anti-DGP) [2]. As a result of the inflammatory process, overgrowth of intestinal crypts and villous atrophy develops [3].
Current knowledge about the aetiopathogenesis of CD clearly shows that it occurs only in people with specific HLA histocompatibility antigens HLA DQ2 or DQ8 [4–6]. They consist of two  and  chains forming homo- and heterozygotes. Histocompatibility antigens HLA-DQ2 have two forms: HLA-DQ 2.2 and HLA-DQ 2.5. The presence of single  or  chains has also been shown [7]. Histocompatibility antigens HLA DQ2 in the healthy population occur in 20–30% of people, and it has been shown that CD will develop in 3–4% of them in the future [8, 9].
It is estimated that 1–3% of the population suffer from CD, 10–15% of whom are not diagnosed accurately [10, 11]. It may be justified by the fact that the symptoms are often unspecific, scant, or may mimic other diseases. Celiac disease can appear at any age with varying symptomatology in children and adults.
There are four different clinical forms of CD: classical, silent, latent, and potential (genetic susceptibility for CD) [12].
The diagnosis of CD is based on clinical symptoms, histopathological criteria, and serological tests. According to current ESPGHAN guidelines [2], it is recommended that serum concentration of anti-tTG IgA and total IgA should be determined first. The use of deamidated gliadin peptide (DGP) tests has emerged in recent years. IgA antibodies against DGP have comparable sensitivity and specificity to anti-tTG. In addition, anti-DGP antibodies have higher sensitivity and specificity for IgG than anti-tTG. Thus anti-DGP may be used in screening for CD and control of gluten-free diet compliance, especially in patients with IgA deficiency [13, 14]. Anti-­endomysial IgA sensitivity is less than that of anti-tTG IgA [14]. Simultaneous determination of two or more antibodies, especially the addition of anti-DGP IgA and anti-DGP IgG to anti-tTG tests, was recently suggested by Schyum and Rumessen [14]. An important element of the CD evaluation is also genetic testing. The current guidelines, both European and American, include the presence of HLA DQ2/DQ8 as necessary for the accurate diagnosis of CD [2, 15].


Irritable bowel syndrome and CD share common manifestations. Gastrointestinal symptoms in the absence of mucosal abnormalities characterise both: IBS and latent/potential CD. Celiac disease must be considered in differential diagnosis of IBS, especially in the poorly controlled group. The aim of the present study was to estimate the prevalence of predispositions to CD in patients with IBS and its subtypes.

Material and methods

The study included 48 patients (40 women, 8 men; average age: 41.1 ±14.6 years) with a diagnosis of IBS based on Rome III criteria. The proportion of patients with IBS-D was 56.25% (n = 27), IBS-C – 29.17% (n = 14), and IBS-M – 14.58% (n = 7). The control group consisted of 20 healthy volunteers matched for age and sex (11 women, 9 men; average age: 38.2 ±14.3 years). Blood samples were taken from all patients to determine the HLA DQ2 and DQ8 antigens by EUROArray® at Euroimmun, Wroclaw, Poland. The presence of only a single chain  of HLA DQ2 was not considered as a positive genetic factor for CD. In each patient serum concentration of antibodies against tissue transglutaminase II (anti-tTG IgA) and deamidated gliadin peptides (anti-DGP IgA and IgG) were measured using ELISA kits. We considered as positive level of anti-tTG three times higher than normal, according to ESPGHAN guidelines [2]. All participants in the study also completed a questionnaire on current gastrointestinal symptoms including the Rome III criteria for diagnosis of IBS.
The study protocol was approved by the Ethics Committee of the Medical University of Lodz. All the participants provided informed consent.


In the study group, the presence of histocompatibility antigens HLA DQ2 or DQ8 was found in 50% of patients (n = 24) with IBS, including 22 patients with the presence of HLA-DQ2 and 3 with HLA-DQ8 (1 IBS-D patient with both antigens). In 31.25% of the patients (n = 15) the presence of the above-mentioned antigens was not detected or only single  chains of DQ2.5 or DQ2.2 was identified – 18.75% (n = 9). As a result of analysis of histocompatibility antigens DQ2, in 7 patients the concomitant presence of both variants of the gene – DQ2.5 and DQ2.2 – was found, in 10 patients only HLA DQ2.5, and in 5 only DQ2.2. In the control group the presence of HLA DQ2 was detected in 4 (20%) patients, including HLA DQ2.2 in 3 and DQ2.5 in 2, and 1 person had 2 gene variants at the same time. Single  chains of DQ2.5 or DQ2.2 were found in 8 healthy patients. HLA DQ8 was not identified in any of the subjects.
The statistical analysis showed that patients with IBS, regardless of the subtype of the disease, significantly more often than healthy controls had the predisposing genetic factors underlying the development of CD (p < 0.05) (Figure 1).
The evaluation assessed the relationship between the presence of histocompatibility antigens and the subtype of IBS. Among patients with IBS-D positive HLA-DQ2/DQ8 was found in 13 (48.15%) patients, with IBS-C in 8 (57.14%), and IBS-M in 3 (42.86%) (Table I). The prevalence of genetic markers did not differ significantly among the patients from those IBS subtypes.
In all subjects the serum level of anti-tTG IgA and anti-DGP IgA and IgG was determined. Among patients with IBS, three times higher than normal levels of anti-tTG (according to ESPGHAN guidelines [2]) were found in 5 (10.42%) patients, including 2 patients with IBS-D, and 3 with IBS-C. Elevated levels of anti-DGP IgA were detected in 4 (8.33%) patients: 1 with IBS-D, 2 with IBS-C, and 1 IBS-M. Anti-DGP IgG was found in 3 (6.25%) patients, among them 2 IBS-D and 1 IBS-C. In only 1 IBS-C patient a simultaneous significant increase in 2 overestimated antibodies was found. In the control group a positive test result for anti-tTG was found in 2 (10%) patients, and no elevated IgA or IgG anti-DGP were detected (Table II). There were no significant differences in the prevalence of anti-tTG IgA and anti-DGP IgA and IgG antibodies among IBS subtypes and the IBS and control group.
Patients with IBS and positive HLA-DQ2/DQ8 reported slightly more gastrointestinal symptoms compared with patients without these genetic markers (p > 0.05). Their most commonly reported symptoms were: urgency for bowel movements, feeling of incomplete evacuation, bloating, and loose stools.
In patients with IBS a concomitant positive result of genetic testing and elevated level of serum antibodies specific to CD was found in 12.5% of patients (n = 6), including 3 with IBS-D and 3 with IBS-C. In the control group there was no such person.


Based on our analysis, patients with IBS significantly more often than healthy subjects had genetic markers predisposing to CD (the presence of HLA DQ2/DQ8 in 50% of patients vs. 20% in the control group). The incidence was not significantly different among the IBS subtypes.
In a study by Wahnschaffe et al. 35% patients with diarrheal form of IBS had HLA-DQ2 [16]. Similar results were also obtained in our analysis, where in patients with IBS-D HLA-DQ2 the incidence amounted to 44.44%. However, in a large prospective multicentre study conducted in the USA in a group of 492 patients with non-constipation predominant IBS (NC-IBS) the incidence of haplotypes DQ2 or DQ8 (46.34%) was lower compared to the control group (52.62%) [17]. A limitation of these studies is the fact that they were carried out only in a subgroup of patients with IBS, and the results cannot be extrapolated to the entire population of those patients, including patients with IBS-C.
Researchers from the Mayo Clinic, USA demonstrated that IBS-D patients positive for HLA-DQ8, or both HLA-DQ2 and HLA-DQ8, have faster small bowel transit than those without such genetic markers. These data confirm the hypothesis that the HLA-DQ subtype is an immunogenetic predisposing factor accelerating small bowel transit after gluten exposure. It has been suggested that it causes symptoms in IBS patients who do not have CD [18]. Further studies confirmed that gluten alters bowel barrier functions in patients with IBS-D, particularly HLADQ2/8-positive. The mechanism of the disorder is reversible with a gluten-free diet [19].
In our study the prevalence of elevated serum levels of CD-specific antibodies among patients with IBS was found in 10.42% patients for anti-tTG IgA, 8.33% for anti-DGP IgA, and 6.25% for anti-DGP IgG. These values were not statistically different compared to the control group (respectively, 10 %, 0%, and 0%). In a study carried out in the years 2007–2009 in Warsaw in a group of 150 patients with IBS diagnosed based on Rome II criteria, 32 (21.3%) patients had elevated anti-tTG antibodies and/or AGAs serum concentration; duodenal mucosa histology in all investigated patients was normal [20].
In a cross-sectional study conducted in 2008–2010 in Southeast Iran, in 5.5% of patients with IBS elevated serum anti-tTG IgA levels were found, particularly in IBS-D subtype (10.5%) [21]. In our study, the highest proportion of patients with elevated anti-tTG antibody titres was observed in the IBS-C group, but the differences were not statistically significant between the IBS subtypes.
In a study by Cash et al. abnormal CD antibodies were found in 7.3% of IBS patients, compared to 4.8% in healthy subjects. In the group of NC-IBS 6.51% had anti-gliadin, 1.22% anti-tTG, and 0.61% antibodies against endomysium (p > 0.05 vs. control for all antibodies). After gastroduodenoscopy with biopsy was performed on them, CD was diagnosed in 0.41% of patients in the NC-IBS and 0.44% in the control group (p > 0.99) [17]. In a study on an Asian population, 18% of a total of 186 IBS patients were positive for anti-DGP IgA, and diarrhoea was the common symptom among them. All patients with positive anti-DGP IgA observed symptom improvement after the application of a gluten-free diet [22].
A gluten-free diet in patients with IBS can bring an improvement in the gastrointestinal symptoms, particularly diarrhoea, which was confirmed in several clinical trials. In the study by Wahnschaffe et al. cited above, in 35% patients with IBS-D HLA-DQ2 was detected, whereas no increased anti-gliadin and anti-tTG levels were found. Nevertheless, the gluten-free diet introduced in them resulted in reduction of symptoms, diarrhoea in particular. The authors explain this as the presence of latent or potential CD in this group [16]. Further studies carried out by the same authors in a group of 145 patients with IBS-D showed that elevated serum levels of IgG antibodies against gliadin and tissue-transglutaminase were detected in 37% and the expression of HLA-DQ2 in 39% of patients. After 6 months of gluten-free diet, decreased stool frequency and relief of gastrointestinal symptoms was observed in 60% of IBS patients who were positive and in 12% who were negative for HLA-DQ2 and coeliac disease-associated serum IgG. According to Wahnschaffe et al., these CD-associated serum and genetic markers can identify likely responders to a gluten-free diet in IBS-D patients [23].
According to our results, a positive result of genetic testing and at the same time elevated level of serum antibodies specific to CD among patients with IBS was found in 12.5% and in none of the control group subjects. In such patients, intestinal biopsy is recommended to confirm the diagnosis of CD. Our study protocol, however, provided non- invasive testing only.
In the study by Korkut et al., in 2% of patients with IBS diagnosed based on the Rome III criteria, elevated levels of anti-gliadin IgG and IgA and anti-tTG IgA were found. The diagnosis of coeliac disease was also confirmed histologically by intestinal biopsy [24]. Similar results were obtained also by El-Salhy et al.; based on histopathological examination of the duodenal mucosa, CD was diagnosed in 0.4% of patients with IBS, all of whom were positive for tissue transglutaminase antibodies (anti-tTG) IgA [25]. A study conducted in Jordan in a group of 742 patients with IBS confirmed CD in 24 (3.23%) patients, based on indications of anti-tTG IgA and intestinal biopsy, with significantly more common CD in IBS-D patients (IBS-D 6.8%, IBS-C 1.68%, IBS-M 2.23%) [26]. While in a study from Iran in a group of 105 IBS patients, CD was confirmed (determination of specific antibodies against endomysium or antibodies against gliadin and intestinal biopsy) in 12 (11.4%) patients [27].
In a study conducted in a group of 200 Polish patients with IBS-D, CD based on serological tests and duodenal biopsy was found in 7% of them (14 of 40 immunologically positive patients) [28].
In the case-control study of 300 subjects fulfilling the Rome II criteria for IBS, Sanders et al. found that the patients with IBS were seven times more likely to have biopsy-proven CD than matched controls. 4.6% of patients with IBS, who tested positive for the antibodies had active CD as compared with 0.66% of the healthy controls [29].
Several studies suggest that the incidence of CD in IBS patients is higher than in the general population: from 0.4% to 11.4% [23–25, 27, 28], especially in IBS-D subtype: 0.41–7% [17, 26, 28]. A meta-analysis by Ford et al. also showed that the prevalence of CD in IBS patients is around four times higher than in the general population [30].
However, there are also studies suggesting that the prevalence of CD in patients with IBS is not higher than that in the general population. Hin et al. conducted a case-finding study of CD (determination of endomysial antibodies followed by duodenal biopsy of those with positive results), and none of 132 patients with IBS had a positive result for CD [31].
In a systematic review by Cash et al. it was confirmed that routine serological testing for CD may be justified in patients meeting the clinical criteria for IBS [32], especially in first-degree relatives of patients with CD [33]. Another analysis conducted in 2004 also showed that the search for CD in patients with IBS can be cost effective [34].


Patients with IBS, regardless of the subtype of the disease, significantly more often than healthy controls have the predisposing genetic factors (HLA DQ2/DQ8) underlying the development of CD. To identify a possible subgroup of IBS patients with latent or potential CD, genetic and serological markers of CD should be investigated. Patients with positive serology as well as HLA DQ2/DQ8 should be carefully evaluated, including gastrointestinal biopsy, and they would probably benefit from the introduction of a gluten-free diet.


The research leading to these results has received funding from the Department of Digestive Tract Diseases statutory financial resources (503/1-002-01/503-01) and grants from the Medical University of Lodz for young scientists (502-03/1-002-01/502-14-148, 502-03/1-002-01/502-14-209).

Conflict of interest

The authors declare no conflict of interest.


1. Drossman DA. Moderator. AGA Clinical Symposium – Rome III: New Criteria for the Functional GI Disorders. Program and Abstract of Digestive Diseases Week; May 20-25. 2006; Los Angeles, California, 461-9.
2. Husby S, Koletzko S, Korponay-Szabó IR, et al. ESPGHAN Working Group on Coeliac Disease Diagnosis; ESPGHAN Gastroenterology Committee; European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012; 54: 136-60.
3. Oberhuber G. Histopathology of celiac disease. Biomed Pharmacother 2000; 54: 368-72.
4. Margaritte-Jeannin P, Babron MC, Bourgey M, et al. HLA-DQ relative risks for coeliac disease in European populations: a study of the European Genetics Cluster on Coeliac Disease. Tissue Antigens 2004; 63: 562-7.
5. Scanlon SA, Murray JA. Update on celiac disease – etiology, differential diagnosis, drug targets, and management advances. Clin Exp Gastroenterol 2011; 4: 297-311.
6. Barker JM, Liu E. Celiac disease: pathophysiology, clinical manifestations, and associated autoimmune conditions. Adv Pediatr 2008; 55: 349-65.
7. Kupfer SS, Jabri B. Pathophysiology of celiac disease. Gastrointest Endosc Clin N Am 2012; 22: 639-60.
8. Mearin ML, Biemond I, Peña AS, et al. HLA-DR phenotypes in Spanish coeliac children: their contribution to the understanding of the genetics of the disease. Gut 1983; 24: 532-7.
9. Hoffenberg EJ, MacKenzie T, Barriga KJ, et al. A prospective study of the incidence of childhood celiac disease. J Pediatr 2003; 143: 308-14.
10. Rostom A, Murray JA, Kagnoff MF. AGA Institute Medical Position Statement on the Diagnosis and Management of Celiac Disease. Gastroenterology 2006; 131: 1977-80.
11. Rewers M. Epidemiology of coeliac disease: what are the prevalence incidence and progression of celiac disease? Gastroenterology 2005; 128 (4 Suppl. 1): 47-51.
12. Iwańczak B, Iwanczak F. New guidelines for diagnosis and treatment of coeliac disease in children and adolescents. Prz Gastroenterol 2012; 7: 185-91.
13. Vermeersch P, Geboes K, Mariën G, et al. Diagnostic performance of IgG anti-deamidated gliadin peptide antibody assays is comparable to IgA anti-tTG in celiac disease. Clin Chim Acta 2010; 411: 931-5.
14. Schyum AC, Rumessen JJ. Serological testing for celiac disease in adults. United European Gastroenterol J 2013; 1: 319-25.
15. Rubio-Tapia A, Hill ID, Kelly CP, et al.; American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol 2013; 108: 656-76.
16. Wahnschaffe U, Ullrich R, Riecken EO, Schulzke JD. Celiac disease-like abnormalities in a subgroup of patients with irritable bowel syndrome. Gastroenterology 2001; 121: 1329-38.
17. Cash BD, Rubenstein JH, Young PE, et al. The prevalence of abnormal celiac antibodies and celiac disease in patients with suspected irritable bowel syndrome: a prospective multi-center US study. Gastroenterology 2011; 141: 1187-93.
18. Vazquez-Roque MI, Camilleri M, Carlson P, et al. HLA-DQ genotype is associated with accelerated small bowel transit in patients with diarrhea-predominant irritable bowel syndrome. Eur J Gastroenterol Hepatol 2011; 23: 481-7.
19. Vazquez-Roque MI, Camilleri M, Smyrk T, et al. A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. Gastroenterology 2013; 144: 903-11.
20. Respondek W, Tomasiuk R, Jarosz M, et al. Is it reasonable to perform serological tests for celiac disease in patients with irritable bowel syndrome? Prz Gastroenterol 2013; 8: 184-90.
21. Bakhshipour A, Nezam SK, Zakeri Z, et al. Coeliac disease in irritable bowel syndrome (Rome III) in Southeast Iran. Arab J Gastroenterol 2012; 13: 24-7.
22. Lu W, Gwee KA, Siah KT, et al. Prevalence of anti-deamidated gliadin peptide antibodies in Asian patients with irritable bowel syndrome. J Neurogastroenterol Motil 2014; 20: 236-41.
23. Wahnschaffe U, Schulzke JD, Zeitz M, et al. Predictors of clinical response to gluten-free diet in patients diagnosed with diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol 2007; 5: 844-50.
24. Korkut E, Bektas M, Oztas E, et al. The prevalence of celiac disease in patients fulfilling Rome III criteria for irritable bowel syndrome. Eur J Intern Med 2010; 21: 389-92.
25. El-Salhy M, Lomholt-Beck B, Gundersen D. The prevalence of celiac disease in patients with irritable bowel syndrome. Mol Med Rep 2011; 4: 403-5.
26. Jadallah KA, Khader YS. Celiac disease in patients with presumed irritable bowel syndrome: a case-finding study. World J Gastroenterol 2009; 15: 5321-5.
27. Shahbazkhani B, Forootan M, Merat S, et al. Coeliac disease presenting with symptoms of irritable bowel syndrome. Aliment Pharmacol Ther 2003; 18: 231-5.
28. Zwolińska-Wcisło M, Galicka-Latała D, Rozpondek P, et al. Frequency of celiac disease and irritable bowel syndrome coexistance and its influence on the disease course. Przegl Lek 2009; 66: 126-9.
29. Sanders DS, Carter MJ, Hurlstone DP, et al. Association of adult coeliac disease with irritable bowel syndrome: a case-control study in patients fulfilling ROME II criteria referred to secondary care. Lancet 2001; 358: 1504-8.
30. Ford AC, Chey WD, Talley NJ, et al. Yield of diagnostic tests for celiac disease in individuals with symptoms suggestive of irritable bowel syndrome: systematic review and meta-analysis. Arch Intern Med 2009; 169: 651-8.
31. Hin H, Bird G, Fisher P, et al. Coeliac disease in primary care: case finding study. BMJ 1999; 318: 164-7.
32. Cash BD, Schoenfeld P, Chey WD. The utility of diagnostic tests in irritable bowel syndrome patients: a systematic review. Am J Gastroenterol 2002; 97: 2812-9.
33. Szawłowska D, Bąk-Romaniszyn L. Family recognition of celiac disease. Prz Gastroenterol 2013; 8: 390-5.
34. Mein SM, Ladabaum U. Serological testing for coeliac disease in patients with symptoms of irritable bowel syndrome: a cost-effectiveness analysis. Aliment Pharmacol Ther 2004; 19: 1199-210.

Received: 20.04.2015
Accepted: 22.06.2015
Copyright: © 2016 Termedia Sp. z o. o. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
© 2017 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe