A similar inverse gene dosage effect was also seen for anti-OmpC prevalence gene in relation to the number of TLR2 mutations. (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 -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 examined 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 potential customers 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. healthy control or CD UC, but also as potential indicators and/or predictors for disease activity/location, disease course/complication, need for medical procedures, and prognosis of therapy. For example, CD patients who are positive in multiple anti-microbial antibodies (ASCA, anti-OmpC, anti-CBir, and anti-I2) have increased risk of having more complicated disease. Patients who are positive in all four of these biomarkers have 11-fold increased risk to develop penetrating and/or stricturing disease[28-32]. CD patients positive with three markers (anti-OmpC, anti-CBir, and anti-I2) are more likely to have small bowel surgery than those who were unfavorable (72% 23%). No comparable association of serotype was found with disease phenotype CEP-28122 of UC[32]. Elevated levels of serological biomarkers were shown to be associated with IBD-susceptible gene variants. Family members of CD patients with NOD2/CARD15 3020insC variant was reported to have increased intestinal permeability, which has been positively associated with elevated serological biomarkers[33,34]. However, reports on this relationship have been inconsistent[35-38], even though more studies offered a positive association between serological biomarkers and susceptible gene variants[32,37,38]. Future studies by impartial groups with larger cohorts, well-defined clinical characteristics and individual populations (such as ethnicity) are necessary to resolve this discrepancy. Other note-worthy aspects of these serological biomarkers include their potential value as subclinical biomarkers and their inherent geographic/ethnic heterogeneity. (1) Indie studies have shown that this prevalence of ASCA positivity is usually significantly higher (20%-25%) in unaffected first-degree relatives of patients with CD[18,39] compared to general healthy populations (0%-10%), indicating a familial association. A much stronger indication that ASCA may be a potential subclinical biomarkers for CD came in 2005. In a serological analysis of a large serum depository, Israeli et al reported that ASCA reactivity was found 38 mo before clinical diagnosis in 32% of the CD patients analyzed[40]; (2) The diagnostic value of serological biomarkers can vary significantly among different ethnic or geographic populations. For example, both ASCA and pANCA were found to be less sensitive in Chinese and Japanese patients[41,42]. On the other hand, positivity of pANCA was shown to be higher in CEP-28122 Mexican-American UC patients: all Mexican-Americans with UC tested experienced positive pANCA compared to only 40% of Caucasians[42]. CEP-28122 These studies suggest that physicians must factor CEP-28122 the patients ethnic background when serological biomarkers are applied in the clinical settings. CEP-28122 At least two dozen non-antibody serum biomarkers have also been reported, including, C-reactive protein, calprotectin, and PMN-elastase, soluble selectins, adhesion molecules, and procalcitonin (PCT)[4,5,43-45]. However, it is necessary to point Rabbit polyclonal to ABHD12B out that most of these markers have not been extensively characterized. Many of them are also elevated in a variety of other inflammatory or pathological conditions with a low specificity to IBD. Therefore, their actual clinical value needs to be further investigated or validated. NEW SEROLOGICAL IBD BIOMARKERS.