摘要
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 character-ization of new serological biomarkers (identifi ed since 2007). These include fi ve new anti-glycan antibodies, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-manobioside IgG (AMCA), and antibod-ies against chemically synthesized (∑) two major oligomannose epitopes, Man α-1,3 Man α-1,2 Man (∑Man3) and Man α-1,3 Man α-1,2 Man α-1,2 Man (∑Man4). 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-likereceptors (TLR) 2 and 4, and β-defensin-1. Further-more, 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 mul-tiplex enzyme-linked immunosorbent assay (ELISA)'s (with an emphasis on cytokine/chemokine profiling). Finally, the prospects of developing more clinically use-ful novel diagnostic algorithms by incorporating new technologies in serological biomarker profiling and integrating multiple biomarkers with bioinformatics analysis/modeling are also discussed.
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 （identifi ed since 2007）. These include fi ve new anti-glycan antibodies, anti-chitobioside IgA （ACCA）, anti-laminaribioside IgG （ALCA）, anti-manobioside IgG （AMCA）, and antibodies against chemically synthesized （∑） two major oligomannose epitopes, Man α-1,3 Man α-1,2 Man （∑Man3） and Man α-1,3 Man α-1,2 Man α-1,2 Man （∑Man4）. 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-likereceptors （TLR） 2 and 4, and β-defensin-1. Further-more, 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.
基金
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
