Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Gastroenterology
Published in: BMC Gastroenterology 1/2012

Open Access 01-12-2012 | Research article

Serum parameters in the spectrum of coeliac disease: beyond standard antibody testing - a cohort study

Authors: Greetje J Tack, Roy L J van Wanrooij, B Mary E Von Blomberg, Hedayat Amini, Veerle M H Coupe, Petra Bonnet, Chris J J Mulder, Marco W J Schreurs

Published in: BMC Gastroenterology | Issue 1/2012

Login to get access

Abstract

Background

Invasive techniques are still required to distinguish between uncomplicated and complicated forms of CD.

Methods

We set out to investigate the potential use of novel serum parameters, including IL-6, IL-8, IL-17, IL-22, sCD25, sCD27, granzyme-B, sMICA and sCTLA-4 in patients diagnosed with active CD, CD on a GFD, Refractory coeliac disease (RCD) type I and II, and enteropathy associated T-cell lymphoma (EATL).

Results

In both active CD and RCDI-II elevated levels of the proinflammatory IL-8, IL-17 and sCD25 were observed. In addition, RCDII patients displayed higher serum levels of soluble granzyme-B and IL-6 in comparison to active CD patients. In contrast, no differences between RCDI and active CD or RCDII were observed. Furthermore, EATL patients displayed higher levels of IL-6 as compared to all other groups.

Conclusions

A series of novel serum parameters reveal distinctive immunological characteristics of RCDII and EATL in comparison to uncomplicated CD and RCDI.
Appendix
Available only for authorised users
Literature
1.
Jabri B, Sollid LM: Tissue-mediated control of immunopathology in coeliac disease. Nat Rev Immunol. 2009, 9 (12): 858-870. 10.1038/nri2670.CrossRefPubMed
2.
Nilsen EM, Jahnsen FL, Lundin KE, Johansen FE, Fausa O, Sollid LM, Jahnsen J, Scott H, Brandtzaeg P: Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease. Gastroenterology. 1998, 115 (3): 551-563. 10.1016/S0016-5085(98)70134-9.CrossRefPubMed
3.
Fernandez S, Molina IJ, Romero P, Gonzalez R, Pena J, Sanchez F, Reynoso FR, Perez-Navero JL, Estevez O, Ortega C, Santamaria M: Characterization of gliadin-specific Th17 cells from the mucosa of celiac disease patients. Am J Gastroenterol. 2011, 106 (3): 528-538. 10.1038/ajg.2010.465.CrossRefPubMed
4.
Monteleone I, Sarra M, Del Vecchio BG, Paoluzi OA, Franze E, Fina D, Fabrizi A, MacDonald TT, Pallone F, Monteleone G: Characterization of IL-17A-producing cells in celiac disease mucosa. J Immunol. 2010, 184 (4): 2211-2218. 10.4049/jimmunol.0901919.CrossRefPubMed
5.
Sapone A, Lammers KM, Mazzarella G, Mikhailenko I, Carteni M, Casolaro V, Fasano A: Differential mucosal IL-17 expression in two gliadin-induced disorders: gluten sensitivity and the autoimmune enteropathy celiac disease. Int Arch Allergy Immunol. 2010, 152 (1): 75-80.CrossRefPubMed
6.
Hue S, Mention JJ, Monteiro RC, Zhang S, Cellier C, Schmitz J, Verkarre V, Fodil N, Bahram S, Cerf-Bensussan N, Caillat-Zucman S: A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease. Immunity. 2004, 21 (3): 367-377. 10.1016/j.immuni.2004.06.018.CrossRefPubMed
7.
Meresse B, Chen Z, Ciszewski C, Tretiakova M, Bhagat G, Krausz TN, Raulet DH, Lanier LL, Groh V, Spies T, Ebert EC, Green PH, Jabri B: Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity. 2004, 21 (3): 357-366. 10.1016/j.immuni.2004.06.020.CrossRefPubMed
8.
Daum S, Cellier C, Mulder CJ: Refractory coeliac disease. Best Pract Res Clin Gastroenterol. 2005, 19 (3): 413-424. 10.1016/j.bpg.2005.02.001.CrossRefPubMed
9.
10.
Verbeek WH, Goerres MS, von Blomberg BM, Oudejans JJ, Scholten PE, Hadithi M, Al-Toma A, Schreurs MW, Mulder CJ: Flow cytometric determination of aberrant intra-epithelial lymphocytes predicts T-cell lymphoma development more accurately than T-cell clonality analysis in Refractory Celiac Disease. Clin Immunol. 2008, 126 (1): 48-56. 10.1016/j.clim.2007.09.002.CrossRefPubMed
11.
Cellier C, Patey N, Mauvieux L, Jabri B, Delabesse E, Cervoni JP, Burtin ML, Guy-Grand D, Bouhnik Y, Modigliani R, Barbier JP, Macintyre E, Brousse N, Cerf-Bensussan N: Abnormal intestinal intraepithelial lymphocytes in refractory sprue. Gastroenterology. 1998, 114 (3): 471-481. 10.1016/S0016-5085(98)70530-X.CrossRefPubMed
12.
Tack GJ, van Wanrooij RL, Langerak AW, Tjon JM, von Blomberg BM, Heideman DA, van BJ, Koning F, Bouma G, Mulder CJ, Schreurs MW: Origin and immunophenotype of aberrant IEL in RCDII patients. Mol Immunol. 2012, 50 (4): 262-270. 10.1016/j.molimm.2012.01.014.CrossRefPubMed
13.
de Bruin PC, Connolly CE, Oudejans JJ, Kummer JA, Jansen W, McCarthy CF, Meijer CJ: Enteropathy-associated T-cell lymphomas have a cytotoxic T-cell phenotype. Histopathology. 1997, 31 (4): 313-317. 10.1046/j.1365-2559.1997.2660862.x.CrossRefPubMed
14.
Al-Toma A, Verbeek WH, Hadithi M, von Blomberg BM, Mulder CJ: Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: retrospective evaluation of single-centre experience. Gut. 2007, 56 (10): 1373-1378. 10.1136/gut.2006.114512.CrossRefPubMedPubMedCentral
15.
Daum S, Ipczynski R, Schumann M, Wahnschaffe U, Zeitz M, Ullrich R: High rates of complications and substantial mortality in both types of refractory sprue. Eur J Gastroenterol Hepatol. 2009, 21 (1): 66-70. 10.1097/MEG.0b013e328307c20c.CrossRefPubMed
16.
Malamut G, Afchain P, Verkarre V, Lecomte T, Amiot A, Damotte D, Bouhnik Y, Colombel JF, Delchier JC, Allez M, Cosnes J, Lavergne-Slove A, Meresse B, Trinquart L, Macintyre E, Radford-Weiss I, Hermine O, Brousse N, Cerf-Bensussan N, Cellier C: Presentation and long-term follow-up of refractory celiac disease: comparison of type I with type II. Gastroenterology. 2009, 136 (1): 81-90. 10.1053/j.gastro.2008.09.069.CrossRefPubMed
17.
Rubio-Tapia A, Kelly DG, Lahr BD, Dogan A, Wu TT, Murray JA: Clinical staging and survival in refractory celiac disease: a single center experience. Gastroenterology. 2009, 136 (1): 99-107. 10.1053/j.gastro.2008.10.013.CrossRefPubMed
18.
Walker-Smith JA, Guandalini S, Schmitz 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 (8): 909-911.CrossRef
19.
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 (10): 1185-1194.CrossRefPubMed
20.
Manavalan JS, Hernandez L, Shah JG, Konikkara J, Naiyer AJ, Lee AR, Ciaccio E, Minaya MT, Green PH, Bhagat G: Serum cytokine elevations in celiac disease: association with disease presentation. Hum Immunol. 2010, 71 (1): 50-57. 10.1016/j.humimm.2009.09.351.CrossRefPubMed
21.
Kerttula TO, Hallstrom O, Maki M: Phenotypical characterization of peripheral blood T cells in patients with coeliac disease: elevation of antigen-primed CD45RO + T lymphocytes. Immunology. 1995, 86 (1): 104-109.PubMedPubMedCentral
22.
Lahat N, Shapiro S, Karban A, Gerstein R, Kinarty A, Lerner A: Cytokine profile in coeliac disease. Scand J Immunol. 1999, 49 (4): 441-446. 10.1046/j.1365-3083.1999.00523.x.CrossRefPubMed
23.
Nilsen EM, Lundin KE, Krajci P, Scott H, Sollid LM, Brandtzaeg P: Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with Th1 or Th0 profile dominated by interferon gamma. Gut. 1995, 37 (6): 766-776. 10.1136/gut.37.6.766.CrossRefPubMedPubMedCentral
24.
Hall RP, Benbenisty KM, Mickle C, Takeuchi F, Streilein RD: Serum IL-8 in patients with dermatitis herpetiformis is produced in response to dietary gluten. J Invest Dermatol. 2007, 127 (9): 2158-2165. 10.1038/sj.jid.5700929.CrossRefPubMed
25.
Blanco A, Garrote JA, Arranz E, Alonso M, Clavo C: Increased serum IL-2R levels in coeliac disease are related to CD4 but not CD8 antigens. J Pediatr Gastroenterol Nutr. 1992, 15 (4): 413-417. 10.1097/00005176-199211000-00008.CrossRefPubMed
26.
Romaldini CC, Barbieri D, Okay TS, Raiz R, Cancado EL: Serum soluble interleukin-2 receptor, interleukin-6, and tumor necrosis factor-alpha levels in children with celiac disease: response to treatment. J Pediatr Gastroenterol Nutr. 2002, 35 (4): 513-517. 10.1097/00005176-200210000-00010.CrossRefPubMed
27.
Srivastava MD, Rossi TM, Lebenthal E: Serum soluble interleukin-2 receptor, soluble CD8 and soluble intercellular adhesion molecule-1 levels in Crohn’s disease, celiac disease, and systemic lupus erythematosus. Res Commun Mol Pathol Pharmacol. 1995, 87 (1): 21-26.PubMed
28.
Fornari MC, Pedreira S, Niveloni S, Gonzalez D, Diez RA, Vazquez H, Mazure R, Sugai E, Smecuol E, Boerr L, Maurino E, Bai JC: Pre- and post-treatment serum levels of cytokines IL-1beta, IL-6, and IL-1 receptor antagonist in celiac disease. Are they related to the associated osteopenia?. Am J Gastroenterol. 1998, 93 (3): 413-418.CrossRefPubMed
29.
Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK: Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006, 441 (7090): 235-238. 10.1038/nature04753.CrossRefPubMed
30.
Strober W, Fuss IJ: Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology. 2011, 140 (6): 1756-1767. 10.1053/j.gastro.2011.02.016.CrossRefPubMedPubMedCentral
31.
Trifari S, Kaplan CD, Tran EH, Crellin NK, Spits H: Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. Nat Immunol. 2009, 10 (8): 864-871. 10.1038/ni.1770.CrossRefPubMed
32.
Brand S, Beigel F, Olszak T, Zitzmann K, Eichhorst ST, Otte JM, Diepolder H, Marquardt A, Jagla W, Popp A, Leclair S, Herrmann K, Seiderer J, Ochsenkuhn T, Goke B, Auernhammer CJ, Dambacher J: IL-22 is increased in active Crohn’s disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol. 2006, 290 (4): G827-G838. 10.1152/ajpgi.00513.2005.CrossRefPubMed
33.
Bodd M, Raki M, Tollefsen S, Fallang LE, Bergseng E, Lundin KE, Sollid LM: HLA-DQ2-restricted gluten-reactive T cells produce IL-21 but not IL-17 or IL-22. Mucosal Immunol. 2010, 3 (6): 594-601. 10.1038/mi.2010.36.CrossRefPubMed
34.
Font J, Pallares L, Martorell J, Martinez E, Gaya A, Vives J, Ingelmo M: Elevated soluble CD27 levels in serum of patients with systemic lupus erythematosus. Clin Immunol Immunopathol. 1996, 81 (3): 239-243. 10.1006/clin.1996.0184.CrossRefPubMed
35.
Tak PP, Hintzen RQ, Teunissen JJ, Smeets TJ, Daha MR, van Lier RA, Kluin PM, Meinders AE, Swaak AJ, Breedveld FC: Expression of the activation antigen CD27 in rheumatoid arthritis. Clin Immunol Immunopathol. 1996, 80 (2): 129-138. 10.1006/clin.1996.0106.CrossRefPubMed
36.
Swaak AJ, Hintzen RQ, Huysen V, van den Brink HG, Smeenk JT: Serum levels of soluble forms of T cell activation antigens CD27 and CD25 in systemic lupus erythematosus in relation with lymphocytes count and disease course. Clin Rheumatol. 1995, 14 (3): 293-300. 10.1007/BF02208342.CrossRefPubMed
37.
Metkar SS, Naresh KN, Manna PP, Srinivas V, Advani SH, Nadkarni JJ: Circulating levels of TNF alpha and TNF receptor superfamily members in lymphoid neoplasia. Am J Hematol. 2000, 65 (2): 105-110. 10.1002/1096-8652(200010)65:2<105::AID-AJH3>3.0.CO;2-R.CrossRefPubMed
38.
Rubin LA, Nelson DL: The soluble interleukin-2 receptor: biology, function, and clinical application. Ann Intern Med. 1990, 113 (8): 619-627.CrossRefPubMed
39.
Tack GJ, Verbeek WH, Van De Water JM, von Blomberg BM, Bhola SL, Ylstra B, Mulder CJ, Schreurs MW: Phenotypic and genomic analysis of an exceptional case of enteropathy associated T-cell lymphoma. Leuk Res. 2010, 34 (8): e183-e189. 10.1016/j.leukres.2010.02.018.CrossRefPubMed
40.
Groh V, Wu J, Yee C, Spies T: Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature. 2002, 419 (6908): 734-738. 10.1038/nature01112.CrossRefPubMed
41.
Salih HR, Antropius H, Gieseke F, Lutz SZ, Kanz L, Rammensee HG, Steinle A: Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia. Blood. 2003, 102 (4): 1389-1396. 10.1182/blood-2003-01-0019.CrossRefPubMed
42.
Kurzrock R, Redman J, Cabanillas F, Jones D, Rothberg J, Talpaz M: Serum interleukin 6 levels are elevated in lymphoma patients and correlate with survival in advanced Hodgkin’s disease and with B symptoms. Cancer Res. 1993, 53 (9): 2118-2122.PubMed
43.
Gustot T, Lemmers A, Louis E, Nicaise C, Quertinmont E, Belaiche J, Roland S, Van GA, Deviere J, Franchimont D: Profile of soluble cytokine receptors in Crohn’s disease. Gut. 2005, 54 (4): 488-495. 10.1136/gut.2004.043554.CrossRefPubMedPubMedCentral
44.
Haghazali M, Molaei M, Mashayekhi R, Zojaji H, Pourhoseingholi MA, Shooshtarizadeh T, Mirsattari D, Zali MR: Proinflammatory cytokines and thrombomodulin in patients with peptic ulcer disease and gastric cancer, infected with Helicobacter pylori. Indian J Pathol Microbiol. 2011, 54 (1): 103-106. 10.4103/0377-4929.77343.CrossRefPubMed
Metadata
Title
Serum parameters in the spectrum of coeliac disease: beyond standard antibody testing - a cohort study
Authors
Greetje J Tack
Roy L J van Wanrooij
B Mary E Von Blomberg
Hedayat Amini
Veerle M H Coupe
Petra Bonnet
Chris J J Mulder
Marco W J Schreurs
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2012
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/1471-230X-12-159

Other articles of this Issue 1/2012

BMC Gastroenterology 1/2012 Go to the issue

Research article

The Zelnorm epidemiologic study (ZEST): a cohort study evaluating incidence of abdominal and pelvic surgery related to tegaserod treatment

Research article

Diabetes, insulin use and Helicobacter pylori eradication: a retrospective cohort study

Research article

Primary Biliary Cirrhosis in a genetically homogeneous population: Disease associations and familial occurrence rates

Research article

Increased proton pump inhibitor and NSAID exposure in irritable bowel syndrome: results from a case-control study

Research article

Endoscopic ultrasound criteria to predict the need for intervention in pancreatic necrosis

Research article

HCV genotype 1a shows a better virological response to antiviral therapy than HCV genotype 1b
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits