Retrospective evaluation of the clinical utility of serological biomarkers in Chinese patients with inflammatory bowel disease: 2-year clinical experience
-
Shulan Zhang
and Yongzhe Li
Abstract
Background:
Antibodies to saccharomyces cerevisiae (ASCA), antibodies to perinuclear anti-neutrophil cytoplasmic (pANCA), pancreatic autoantibodies (PAB) and antibodies against intestinal goblet cells (GAB) are important in diagnosing Crohn’s disease (CD) and ulcerative colitis (UC). However, little is known about their diagnostic value in real clinical practice in China. This retrospective study aimed to present our 2-year clinical experience with those biomarkers in diagnosis of CD and UC.
Methods:
A total of 140 patients with UC, 128 patients with CD, and 224 patients with intestinal associated diseases as disease controls were included. Serum ASCA were determined by ELISA. Serum pANCA, GAB, and PAB were tested by indirect immunofluorescent assay. Retrospective review of laboratory results and clinical information was performed.
Results:
ASCA and ASCA+/pANCA− showed poor abilities in differentiating CD from UC, CD from intestinal Behçet’s disease (BD), or CD from intestinal tuberculosis (ITB). In contrast, PAB exhibited good capacities in differentiating CD from UC, CD from intestinal BD, and CD from ITB. IgG pANCA demonstrated a high sensitivity and specificity in differentiating UC from CD. pANCA+/ASCA− or pANCA+/PAB− displayed a high sensitivity and specificity in differentiating UC from CD. GAB showed poor potential in differentiating UC from CD. PAB were positively correlated with early disease onset, ileocolonic disease, and perianal disease in CD patients.
Conclusions:
Our data suggest that pANCA and PAB are helpful in diagnosis of UC and CD, respectively, while ASCA and GAB were not. Our findings indicate a clear need for additional biomarkers for diagnosis of CD in China.
Acknowledgments
We thank all the people from the Department of Rheumatology and Clinical Immunology and Department of Gastroenterology, PUMCH, for their assistance during this study.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. SZ, JL, FZ, QJ, and YZ designed the study. SZ, JL, JL, ZW, CH, PL, and CD performed the experiments. SZ, QJ, and YZ wrote the manuscript.
Research funding: This work was supported in part by the National Natural Science Foundation of China Grants No. 81373188, 81172857 (to YL), 81302592 (to SZ), the National Science Technology Pillar Program in the 12nd Five-year Plan No. 2014BAI07B00, the capital health research and development of special grants No. 2014-1-4011 (to YL), and the Shanxi Scholarship council of China No. 2014-079 (to JL), the Chinese National High Technology Research and Development Program, Ministry of Science and Technology Grants, (Grant/Award Number: ‘2011AA02A113’).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med 2009;361:2066–78.10.5005/jp/books/11070_14Search in Google Scholar
2. Fakhoury M, Negrulj R, Mooranian A, Al-Salami H. Inflammatory bowel disease: clinical aspects and treatments. J Inflamm Res 2014;7:113–20.10.2147/JIR.S65979Search in Google Scholar
3. Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet 2007;369:1627–40.10.1016/S0140-6736(07)60750-8Search in Google Scholar
4. Almadi MA, Ghosh S, Aljebreen AM. Differentiating intestinal tuberculosis from Crohn’s disease: a diagnostic challenge. Am J Gastroenterol 2009;104:1003–12.10.1038/ajg.2008.162Search in Google Scholar PubMed
5. Li Y, Zhang LF, Liu XQ, Wang L, Wang X, Wang J, et al. The role of in vitro interferonγ-release assay in differentiating intestinal tuberculosis from Crohn’s disease in China. J Crohns Colitis 2012;6:317–23.10.1016/j.crohns.2011.09.002Search in Google Scholar PubMed
6. Papp M, Lakatos PL. Serological studies in inflammatory bowel disease: how important are they? Curr Opin Gastroenterol 2014;30:359–64.10.1097/MOG.0000000000000076Search in Google Scholar PubMed
7. Laass MW, Roggenbuck D, Conrad K. Diagnosis and classification of Crohn’s disease. Autoimmun Rev 2014;13:467–71.10.1016/j.autrev.2014.01.029Search in Google Scholar PubMed
8. Conrad K, Roggenbuck D, Laass MW. Diagnosis and classification of ulcerative colitis. Autoimmun Rev 2014;13:463–6.10.1016/j.autrev.2014.01.028Search in Google Scholar PubMed
9. Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl 1989;170:2–610.3109/00365528909091339Search in Google Scholar PubMed
10. Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 2005;19:5A-36A.10.1155/2005/269076Search in Google Scholar PubMed
11. Zhang S, Wu Z, Luo J, Ding X, Hu C, Li P, et al. Diagnostic Potential of Zymogen Granule Glycoprotein 2 Antibodies as Serologic Biomarkers in Chinese Patients With Crohn Disease. Medicine (Baltimore) 2015;94:e1654.10.1097/MD.0000000000001654Search in Google Scholar
12. Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn’s disease activity index. National Cooperative Crohn’s Disease Study. Gastroenterology 1976;70:439–44.10.1016/S0016-5085(76)80163-1Search in Google Scholar
13. Walmsley RS, Ayres RC, Pounder RE, Allan RN. A simple clinical colitis activity index. Gut 1998;43:29–32.10.1136/gut.43.1.29Search in Google Scholar PubMed PubMed Central
14. Reese GE, Constantinides VA, Simillis C, Darzi AW, Orchard TR, Fazio VW, et al. Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease. Am J Gastroenterol 2006;101:2410–22.10.1111/j.1572-0241.2006.00840.xSearch in Google Scholar PubMed
15. Quinton JF, Sendid B, Reumaux D, Duthilleul P, Cortot A, Grandbastien B, et al. Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut 1998;42:788–91.10.1136/gut.42.6.788Search in Google Scholar PubMed PubMed Central
16. Saibeni S, Folli C, de Franchis R, Borsi G, Vecchi M. Diagnostic role and clinical correlates of anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (p-ANCA) in Italian patients with inflammatory bowel diseases. Dig Liver Dis 2003;35:862–8.10.1016/j.dld.2003.07.001Search in Google Scholar PubMed
17. Bogdanos DP, Rigopoulou EI, Smyk DS, Roggenbuck D, Reinhold D, Forbes A, et al. Diagnostic value, clinical utility and pathogenic significance of reactivity to the molecular targets of Crohn’s disease specific-pancreatic autoantibodies. Autoimmun Rev 2011;11:143–8.10.1016/j.autrev.2011.09.004Search in Google Scholar PubMed
18. Li J, Jia H, Cai X, Zhong H, Feng Q, Sunagawa S, et al. An integrated catalog of reference genes in the human gut microbiome. Nat Biotechnol 2014;32:834–41.10.1038/nbt.2942Search in Google Scholar PubMed
19. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007;448:427–34.10.1038/nature06005Search in Google Scholar PubMed
20. Makharia GK, Sachdev V, Gupta R, Lal S, Pandey RM. Anti-Saccharomyces cerevisiae antibody does not differentiate between Crohn’s disease and intestinal tuberculosis. Dig Dis Sci 2007;52:33–9.10.1007/s10620-006-9527-0Search in Google Scholar PubMed
21. Kim YS, Kim YH, Kim WH, Kim JS, Park YS, Yang SK, et al. Diagnostic utility of anti-Saccharomyces cerevisiae antibody (ASCA) and Interferon-γ assay in the differential diagnosis of Crohn’s disease and intestinal tuberculosis. Clin Chim Acta 2011;412:1527–32.10.1016/j.cca.2011.04.029Search in Google Scholar PubMed
22. Ashorn S, Raukola H, Välineva T, Ashorn M, Wei B, Braun J, et al. Elevated serum anti-Saccharomyces cerevisiae, anti-I2 and anti-OmpW antibody levels in patients with suspicion of celiac disease. J Clin Immunol. 2008;28:486–94.10.1007/s10875-008-9200-9Search in Google Scholar PubMed PubMed Central
23. Granito A, Muratori L, Muratori P, Guidi M, Lenzi M, Bianchi FB, et al. Anti-saccharomyces cerevisiae antibodies (ASCA) in coeliac disease. Gut. 2006;55:296.Search in Google Scholar
24. Fresko I, Hamuryudan V, Demir M, Hizli N, Sayman H, Melikoğlu M, et al. Intestinal permeability in Behçet’s syndrome. Ann Rheum Dis. 2001;60:65–6.10.1136/ard.60.1.65Search in Google Scholar PubMed PubMed Central
25. DuPont AW. Postinfectious irritable bowel syndrome. Clin Infect Dis 2008;46:594–9.10.1086/526774Search in Google Scholar PubMed
26. Pavlidis P, Komorowski L, Teegen B, Liaskos C, Koutsoumpas AL, Smyk DS, et al. Diagnostic and clinical significance of Crohn’s disease-specific pancreatic anti-GP2 and anti-CUZD1 antibodies. Clin Chem Lab Med 2016;54:249–56.10.1515/cclm-2015-0376Search in Google Scholar PubMed
27. Roggenbuck D, Reinhold D, Schierack P, Bogdanos DP, Conrad K, Laass MW. Crohn’s disease specific pancreatic antibodies: clinical and pathophysiological challenges. Clin Chem Lab Med 2014;52:483–94.10.1515/cclm-2013-0801Search in Google Scholar PubMed
28. Bonneau J, Dumestre-Perard C, Rinaudo-Gaujous M, Genin C, Sparrow M, Roblin X, et al. Systematic review: new serological markers (anti-glycan, anti-GP2, anti-GM-CSF Ab) in the prediction of IBD patient outcomes. Autoimmun Rev 2015;14:231–45.10.1016/j.autrev.2014.11.004Search in Google Scholar PubMed
29. Klebl FH, Bataille F, Huy C, Hofstädter F, Schölmerich J, Rogler G. Association of antibodies to exocrine pancreas with subtypes of Crohn’s disease. Eur J Gastroenterol Hepatol 2005;17:73–7.10.1097/00042737-200501000-00015Search in Google Scholar PubMed
30. Seibold F, Weber P, Jenss H, Wiedmann KH. Antibodies to a trypsin sensitive pancreatic antigen in chronic inflammatory bowel disease: specific markers for a subgroup of patients with Crohn’s disease. Gut 1991;32:1192–7.10.1136/gut.32.10.1192Search in Google Scholar PubMed PubMed Central
31. Lawrance IC, Hall A, Leong R, Pearce C, Murray K. A comparative study of goblet cell and pancreatic exocine autoantibodies combined with ASCA and pANCA in Chinese and Caucasian patients with IBD. Inflamm Bowel Dis 2005;11:890–7.10.1097/01.MIB.0000182872.76434.8cSearch in Google Scholar PubMed
32. Nisihara RM, de Carvalho WB, Utiyama SR, Amarante H, Baptista ML. Diagnostic role and clinical association of ASCA and ANCA in Brazilian patients with inflammatory bowel disease. Dig Dis Sci 2010;55:2309–15.10.1007/s10620-009-0998-7Search in Google Scholar PubMed
33. Lakatos PL, Altorjay I, Szamosi T, Palatka K, Vitalis Z, Tumpek J, et al. Pancreatic autoantibodies are associated with reactivity to microbial antibodies, penetrating disease behavior, perianal disease, and extraintestinal manifestations, but not with NOD2/CARD15 or TLR4 genotype in a Hungarian IBD cohort. Inflamm Bowel Dis 2009;15:365–74.10.1002/ibd.20778Search in Google Scholar PubMed
34. Kovacs M, Lakatos PL, Papp M, Jacobsen S, Nemes E, Polgar M, et al. Pancreatic autoantibodies and autoantibodies against goblet cells in pediatric patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2012;55:429–35.10.1097/MPG.0b013e318256b516Search in Google Scholar PubMed
35. Desplat-Jégo S, Johanet C, Escande A, Goetz J, Fabien N, Olsson N, et al. Update on Anti-Saccharomyces cerevisiae antibodies, anti-nuclear associated anti-neutrophil antibodies and antibodies to exocrine pancreas detected by indirect immunofluorescence as biomarkers in chronic inflammatory bowel diseases: results of a multicenter study. World J Gastroenterol 2007;13:2312–8.10.3748/wjg.v13.i16.2312Search in Google Scholar PubMed PubMed Central
36. Michaels MA, Jendrek ST, Korf T, Nitzsche T, Teegen B, Komorowski L, et al. Pancreatic Autoantibodies Against CUZD1 and GP2 Are Associated with Distinct Clinical Phenotypes of Crohn’s Disease. Inflamm Bowel Dis 2015;21:2864–72.10.1097/MIB.0000000000000564Search in Google Scholar PubMed
37. Zhang Z, Li C, Zhao X, Lv C, He Q, Lei S, et al. Anti-Saccharomyces cerevisiae antibodies associate with phenotypes and higher risk for surgery in Crohn’s disease: a meta-analysis. Dig Dis Sci 2012;57:2944–54.10.1007/s10620-012-2244-ySearch in Google Scholar PubMed
©2017 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- Biotin interference on immunoassay methods: sporadic cases or hidden epidemic?
- Reviews
- False biochemical diagnosis of hyperthyroidism in streptavidin-biotin-based immunoassays: the problem of biotin intake and related interferences
- Vitamin K plasma levels determination in human health
- Mini Review
- Point-of-care testing INR: an overview
- Opinion Paper
- Could accreditation bodies facilitate the implementation of medical guidelines in laboratories?
- Genetics and Molecular Diagnostics
- QMPSF is sensitive and specific in the detection of NPHP1 heterozygous deletions
- General Clinical Chemistry and Laboratory Medicine
- High-dose biotin therapy leading to false biochemical endocrine profiles: validation of a simple method to overcome biotin interference
- Multicenter performance evaluation of a second generation cortisol assay
- A rapid UPLC-MS/MS assay for the simultaneous measurement of fluconazole, voriconazole, posaconazole, itraconazole, and hydroxyitraconazole concentrations in serum
- A microplate assay to measure classical and alternative complement activity
- Serological diagnosis and prognosis of severe acute pancreatitis by analysis of serum glycoprotein 2
- Retrospective evaluation of the clinical utility of serological biomarkers in Chinese patients with inflammatory bowel disease: 2-year clinical experience
- Infrared analysis of lipoproteins in the detection of alcohol biomarkers
- Coexistence of anti-β2-glycoprotein I domain I and anti-phosphatidylserine/prothrombin antibodies suggests strong thrombotic risk
- Antiphosphatidylserine/prothrombin antibodies as biomarkers to identify severe primary antiphospholipid syndrome
- Cardiovascular Diseases
- The impact of admission neutrophil-to-platelet ratio on in-hospital and long-term mortality in patients with infective endocarditis
- Letters to the Editor
- Biotin interference in immunoassays mimicking subclinical Graves’ disease and hyperestrogenism: a case series
- A simple method to detect biotin interference on immunoassays
- Proposed classification for a variant of Kounis syndrome
- Lyophilized hemoglobin E control material for the dichlorophenol-indophenol (DCIP) test
- Procalcitonin variation before and after 100-km ultramarathon
- Preliminary study in specific activity of molecular components in allergy: implications for diagnostics and relationship with disease severity
- A 2-min at 4500 g rather than a 15-min at 2200 g centrifugation does not impact the reliability of 10 critical coagulation assays
- Immunoassay interference caused by heterophilic antibodies interacting with biotin
- Red blood cell distribution width and mean platelet volume are potential prognostic indices for patients with primary biliary cirrhosis
- Neutrophil CD64 molecule expression can predict bloodstream infection in septic shock patients
Articles in the same Issue
- Frontmatter
- Editorial
- Biotin interference on immunoassay methods: sporadic cases or hidden epidemic?
- Reviews
- False biochemical diagnosis of hyperthyroidism in streptavidin-biotin-based immunoassays: the problem of biotin intake and related interferences
- Vitamin K plasma levels determination in human health
- Mini Review
- Point-of-care testing INR: an overview
- Opinion Paper
- Could accreditation bodies facilitate the implementation of medical guidelines in laboratories?
- Genetics and Molecular Diagnostics
- QMPSF is sensitive and specific in the detection of NPHP1 heterozygous deletions
- General Clinical Chemistry and Laboratory Medicine
- High-dose biotin therapy leading to false biochemical endocrine profiles: validation of a simple method to overcome biotin interference
- Multicenter performance evaluation of a second generation cortisol assay
- A rapid UPLC-MS/MS assay for the simultaneous measurement of fluconazole, voriconazole, posaconazole, itraconazole, and hydroxyitraconazole concentrations in serum
- A microplate assay to measure classical and alternative complement activity
- Serological diagnosis and prognosis of severe acute pancreatitis by analysis of serum glycoprotein 2
- Retrospective evaluation of the clinical utility of serological biomarkers in Chinese patients with inflammatory bowel disease: 2-year clinical experience
- Infrared analysis of lipoproteins in the detection of alcohol biomarkers
- Coexistence of anti-β2-glycoprotein I domain I and anti-phosphatidylserine/prothrombin antibodies suggests strong thrombotic risk
- Antiphosphatidylserine/prothrombin antibodies as biomarkers to identify severe primary antiphospholipid syndrome
- Cardiovascular Diseases
- The impact of admission neutrophil-to-platelet ratio on in-hospital and long-term mortality in patients with infective endocarditis
- Letters to the Editor
- Biotin interference in immunoassays mimicking subclinical Graves’ disease and hyperestrogenism: a case series
- A simple method to detect biotin interference on immunoassays
- Proposed classification for a variant of Kounis syndrome
- Lyophilized hemoglobin E control material for the dichlorophenol-indophenol (DCIP) test
- Procalcitonin variation before and after 100-km ultramarathon
- Preliminary study in specific activity of molecular components in allergy: implications for diagnostics and relationship with disease severity
- A 2-min at 4500 g rather than a 15-min at 2200 g centrifugation does not impact the reliability of 10 critical coagulation assays
- Immunoassay interference caused by heterophilic antibodies interacting with biotin
- Red blood cell distribution width and mean platelet volume are potential prognostic indices for patients with primary biliary cirrhosis
- Neutrophil CD64 molecule expression can predict bloodstream infection in septic shock patients