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Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Sep 7, 2008; 14(33): 5115-5124
Published online Sep 7, 2008. doi: 10.3748/wjg.14.5115
New serological biomarkers of inflammatory bowel disease
Xuhang Li, Laurie Conklin, Philip Alex
Xuhang Li, Laurie Conklin, Philip Alex, Division of Gastro-enterology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore MD 21205, United States
Laurie Conklin, Division of Gastroenterology and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore MD 21205, United States
Author contributions: Li X and Alex P wrote and revised the article; Conklin L helped critical review and provided suggestions; Li X finalized the revision.
Supported by Broad Medical Research Program, No. IBD-0119R; NIH/NIDDK grant, No. 5R21DK77064; NIH/NIDDK, No. KO1-DK62264; NIH Ruth L. Kirschstein National Research Service Awards, Proctor & Gamble Investigator Initiated Grants
Correspondence to: Dr. Xuhang Li, Division of Gastro-enterology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave, 918 Ross Research Bldg, Baltimore MD 21205, United States.
Telephone: +1-443-2874804 Fax: +1-410-9559677
Received: June 27, 2008
Revised: August 25, 2008
Accepted: September 2, 2008
Published online: September 7, 2008

Serological biomarkers in inflammatory bowel disease (IBD) are a rapidly expanding list of non-invasive tests for objective assessments of disease activity, early diagnosis, prognosis evaluation and surveillance. This review summarizes both old and new biomarkers in IBD, but focuses on the development and characterization of new serological biomarkers (identified since 2007). These include five new anti-glycan antibodies, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-manobioside IgG (AMCA), and antibodies against chemically synthesized (Σ) two major oligomannose epitopes, Man α-1,3 Man α-1,2 Man (ΣMan3) and Man α-1,3 Man α-1,2 Man α-1,2 Man (ΣMan4). These new biomarkers serve as valuable complementary tools to existing biomarkers not only in differentiating Crohn’s disease (CD), ulcerative colitis (UC), normal and other non-IBD gut diseases, but also in predicting disease involvement (ileum vs colon), IBD risk (as subclinical biomarkers), and disease course (risk of complication and surgery). Interestingly, the prevalence of the antiglycan antibodies, including anti-Saccharomyces cerevisiae antibodies (ASCA), ALCA and AMCA, was found to be associated with single nucleotide polymorphisms (SNPs) of IBD susceptible genes such as NOD2/CARD15, NOD1/CARD4, toll-like receptors (TLR) 2 and 4, and β-defensin-1. Furthermore, a gene dosage effect was observed: anti-glycan positivity became more frequent as the number of NOD2/CARD15 SNPS increased. Other new serum/plasma IBD biomarkers reviewed include ubiquitination factor E4A (UBE4A), CXCL16 (a chemokine), resistin, and apolipoprotein A-IV. This review also discusses the most recent studies in IBD biomarker discovery by the application of new technologies such as proteomics, fourier transform near-infrared spectroscopy, and multiplex enzyme-linked immunosorbent assay (ELISA)’s (with an emphasis on cytokine/chemokine profiling). Finally, the prospects of developing more clinically useful novel diagnostic algorithms by incorporating new technologies in serological biomarker profiling and integrating multiple biomarkers with bioinformatics analysis/modeling are also discussed.

Keywords: Serological biomarkers, Inflammatory bowel disease, Ulcerative colitis, Crohn’s disease, Anti-chitobioside IgA, Anti-laminaribioside IgG, Anti-manobioside IgG, Anti-synthetic mannoside antibodies, Multiplex enzyme-linked immunosorbent assay, Proteomics