Moderate performance of serum S100A12, in distinguishing inflammatory bowel disease from irritable bowel syndrome

<p>Abstract</p> <p>Background</p> <p>S100A12, a calcium-binding proinflammatory protein secreted by granulocytes, has been associated with different diseases of inflammatory origin, including inflammatory bowel disease (IBD). In this study, the utility of serum S100A12, in discriminating IBD from irritable bowel syndrome (IBS), was tested.</p> <p>Methods</p> <p>S100A12 serum levels were determined in 64 patients with ulcerative colitis (UC), 64 with Crohn's disease (CD) and 73 with IBS, by means of an enzyme-linked immunosorbent assay. S100A12 serum levels were evaluated with respect to the levels of known inflammatory markers and patients' characteristics.</p> <p>Results</p> <p>The median values of serum S100A12 levels were 68.2 ng/mL (range: 43.4-147.4) in UC, 70 ng/mL (41.4-169.8) in CD and 43.4 ng/mL (34.4-74.4) in IBS patients. UC and CD patients had significantly higher serum S100A12 levels compared to IBS patients (<it>P </it>= 0.001 for both comparisons). Moreover, a cut-off for serum S100A12 levels of 54.4 ng/mL could predict both UC and CD with a 66.7% sensitivity and a 64.4% specificity. The area under curve was estimated at 0.67 with a 95% confidence interval of 0.60-0.75 (<it>P </it>< 0.001). Considering standard activity indices, higher serum S100A12 levels in active compared to inactive IBD were observed, although the recorded difference did not reach statistical significance. C-reactive protein (CRP) and serum amyloid A (SAA) levels, showed a statistically significant positive correlation with S100A12 (r = 0.39, <it>P </it>= 0.001 and r = 0.23, <it>P </it>= 0.02 respectively).</p> <p>Conclusions</p> <p>Increased levels of circulating S100A12 are found in IBD, compared to IBS. When used to distinguish IBD from IBS adult patients, serum S100A12 levels exhibit moderate performance. On the other hand, serum S100A12 may serve as an inflammatory marker in IBD, since it is well correlated with CRP and SAA.</p

Angiogenic factors in inflammatory bowel diseases

In this study, we evaluated serum TIMP-1, TIMP-2, TIMP-4, PDGF-AA, PDGF-BB and PDGF-AB levels in IBD patients, in comparison with healthy controls (HC). UC and CD patients had significantly higher serum TIMP-1 levels when compared to HC. Mean serum TIMP-1 levels were significantly higher in patients with active IBD in comparison with patients with inactive disease. Moreover, males showed significantly higher mean serum TIMP-1 levels compared to females. Serum TIMP-2 levels remained unchanged. UC and CD patients had significantly lower serum TIMP-4 levels when compared to HC. Mean serum TIMP-4 levels were significantly lower in males compared to females. UC and CD patients had significantly higher serum PDGF-AA levels when compared to HC. Mean serum PDGF-BB levels were significantly higher in patients with active IBD in comparison with patients with inactive disease. Serum PDGF-AB levels remained unchanged. Mean serum PDGF-AA, -BB and -AB levels were significantly lower in older compared to young people. Serum TIMP-1 and serum PDGF-BB may be useful markers of disease activity in IBD. Gender tends to influence TIMP-1 and TIMP-4 serum levels. Aging tends to influence PDGF-AA, -BB and -AB serum levels. These findings bring into question the potential role of TIMPs and PDGFs in IBD, emphasizing the need for further studies on this subject.Στην παρούσα μελέτη, εκτιμήσαμε τα επίπεδα ορού των ιστικών αναστολέων μεταλλοπρωτεϊνασών TIMP-1, TIMP-2 και TIMP-4 και των αυξητικών παραγόντων προερχόμενων από τα αιμοπετάλια PDGF-AA, PDGF-BB και PDGF-AB σε ασθενείς με ιδιοπαθείς φλεγμονώδεις εντεροπάθειες (ΙΦΕΝ) σε σχέση με υγιείς μάρτυρες (ΥΜ). Οι πάσχοντες με ΙΦΕΝ είχαν στατιστικώς σημαντικά υψηλότερα επίπεδα ορού TIMP-1 σε σχέση με τους ΥΜ. Τα επίπεδα ορού του TIMP-1 στους πάσχοντες με ενεργό νόσο ήταν στατιστικώς σημαντικά υψηλότερα σε σχέση με τους πάσχοντες με ανενεργό νόσο. Οι άνδρες της μελέτης είχαν στατιστικώς σημαντικά υψηλότερα επίπεδα ορού TIMP-1 σε σχέση με τις γυναίκες. Δεν παρατηρήθηκαν μεταβολές στατιστικώς σημαντικές στα επίπεδα ορού TIMP-2 μεταξύ πασχόντων και υγιών μαρτύρων. Οι πάσχοντες με ΙΦΕΝ είχαν στατιστικώς σημαντικά χαμηλότερα επίπεδα ορού TIMP-4 σε σχέση με τους υγιείς μάρτυρες. Οι άνδρες της μελέτης είχαν στατιστικώς σημαντικά χαμηλότερα επίπεδα ορού TIMP-4 σε σχέση με τις γυναίκες. Οι πάσχοντες με ΙΦΕΝ είχαν στατιστικώς σημαντικά υψηλότερα επίπεδα ορού PDGF-AA σε σχέση με τους ΥΜ. Τα επίπεδα ορού του PDGF-BB στους πάσχοντες με ενεργό νόσο ήταν στατιστικώς σημαντικά υψηλότερα σε σχέση με τους πάσχοντες με ανενεργό νόσο. Δεν παρατηρήθηκε στατιστικώς σημαντική διαφορά στα επίπεδα ορού PDGF-AB μεταξύ πασχόντων και υγιών μαρτύρων. Παρατηρήθηκε στατιστικώς σημαντική αρνητική συσχέτιση των επιπέδων ορού PDGF-AA, -BB και -ΑΒ με την ηλικία. Τα επίπεδα ορού των TIMP-1 και PDGF-BB πιθανώς μπορούν να χρησιμοποιηθούν ως δείκτης δραστηριότητας της νόσου στους ασθενείς με ΙΦΕΝ. Το φύλο πιθανώς επηρεάζει τα επίπεδα ορού των TIMP-1και TIMP-4. Η ηλικία πιθανώς επηρεάζει τα επίπεδα ορού των PDGF-AA, -BB και -ΑΒ. Δεδομένου ότι οι μέχρι τώρα πληροφορίες μας για το ρόλο των TIMPs και των PDGFs στις ΙΦΕΝ δεν είναι πολλές, τα παραπάνω ευρήματα θα πρέπει να επιβεβαιωθούν με περαιτέρω έρευνα

Imbalance of tissue inhibitors of metalloproteinases (TIMP)-1 and-4 serum levels, in patients with inflammatory bowel disease

Background: Tissue inhibitors of metalloproteinases (TIMPs) play a key role in tissue degradation and remodeling. Since chronic inflammation is associated with tissue remodeling in inflammatory bowel disease (IBD), we evaluated serum TIMP-1 and TIMP-4 levels in IBD patients, in comparison with healthy controls (HC). Methods: TIMP-1, TIMP-2 and TIMP-4 serum levels were determined in 53 patients with ulcerative colitis (UC), 52 patients with Crohn's disease (CD) and 50 HC, by means of commercially available enzyme-linked immunosorbent assays. The levels of TIMPs were evaluated with regard to the levels of inflammatory markers, such as C reactive protein (CRP) and serum amyloid A (SAA) and the clinical characteristics of patients, so that potential correlations could be recorded. Results: Mean serum TIMP-1 levels were 414.9 +/- 17.6 ng/mL in UC patients, 446.1 +/- 22.8 ng/mL in CD patients and 296.5 +/- 20.6 ng/mL in HC. UC and CD patients had significantly higher serum TIMP-1 levels when compared to HC, (p 0.05 in all cases). Mean serum TIMP-4 levels were 1761.2 +/- 67.7 pg/mL in UC patients, 1708.1 +/- 73.4 pg/mL in CD patients and 5573.4 +/- 1246.3 pg/mL in HC. UC and CD patients had significantly lower serum TIMP-4 levels when compared to HC (p = 0.008 and p = 0.02 respectively). Mean serum TIMP-4 levels were significantly lower in males (2772.9 pg/mL), compared to females (3299.0 pg/mL, p = 0.01). In addition, CRP levels showed a statistically significant correlation with TIMP-1 (r = 0.247, p = 0.01), and TIMP-4 levels (r = 0.217, p = 0.03). Similarly, there was a statistically significant correlation between SAA levels and both TIMP-1 (r = 0.264, p = 0.008) and TIMP-4 serum levels (r = 0.212, p = 0.03). Conclusion: An imbalance between TIMP-1 and TIMP-4 serum levels is present in IBD patients. TIMP-1 levels could be used not only for diagnostic purposes but also for the assessment of activity in IBD. Gender tends to influence TIMP-1 and TIMP-4 serum levels. These new findings bring into question the potential role of TIMPs in IBD, thus underlining the need for future studies which could offer new insight into this matter

Readressing the Role of Toll-Like Receptor-4 Alleles in Inflammatory Bowel Disease: Colitis, Smoking, and Seroreactivity

Toll-like receptor (TLR) polymorphisms, and especially TLR-4 Asp299Gly and TLR-4 Thr399Ile, have been linked with Crohn's disease (CD) and to a lesser extent with ulcerative colitis (UC), CD behavior, and compromised seroreactivity to microbial antigens. Available data, however, are conflicting. To address these issues, the distribution of TLR-4 polymorphic alleles was assessed in patients with UC, CD, and healthy controls (HC), considering patient and disease characteristics as well as related serological markers. TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms were determined in 187 UC and 163 CD patients and 274 randomly selected HC. C reactive protein, anti-Saccharomyces cerevisiae mannan antibodies, anti-mannobioside carbohydrate antibodies, anti-laminariobioside carbohydrate antibodies IgG, and anti-chitobioside carbohydrate antibodies (ACCA) IgA levels were also assessed. UC and especially pancolitis patients carried the mutant alleles more frequently compared to CD patients and HC or UC patients with different disease extents (P = 0.002 and P < 0.0001, respectively). Involvement of the colon was more frequent in CD patients with mutant TLR-4 compared to those with wild-type alleles (P = 0.004). Levels and positivity rates of ACCA IgA were lower in inflammatory bowel disease (IBD) patients carrying the mutant compared to those with wild-type alleles (0.075 < P < 0.05). Despite the mutant TLR-4 predisposition for UC pancolitis, smoking was associated with more limited disease (P < 0.001). The presence of TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms is related to UC pancolitis, involvement of the colon in CD, and lower ACCA IgA levels. Smoking reduces the extent of UC, even in the presence of mutant alleles