Marker For Ulcerative Colitis Research Articles

Phlorotannins Isolated from Eisenia bicyclis and Lactobacillus casei Ameliorate Dextran Sulfate Sodium-Induced Colitis in Mice through the AhR Pathway

Ulcerative colitis (UC), an inflammatory bowel disease (IBD) linked to colon cancer, needs effective natural preventive and therapeutic strategies to alleviate its clinical course. This study investigated the combined effects of phlorotannins (TAs) isolated from Eisenia bicyclis (E. bicyclis) and Lactobacillus casei (LC) on inflammatory markers in UC, with a focus on the aryl hydrocarbon receptor (AhR) axis. In vitro experiments revealed anti-inflammatory effects of the phlorotannin fraction isolated from E. bicyclis, especially in synergy with LC. In vivo experiments showed that a synbiotic combination of TAs and LC mitigated DSS-induced colitis and reduced intestinal shortening and splenic hypertrophy. The TA and LC combination suppressed inflammatory factors (IL-6, TNF-α, Lipocalin 2), while activating tight junction genes (Muc2, Zo-1, Occludin, and Claudin1) and enhancing antioxidant capacity (Nrf2 and Nqo1 genes). Activation of the AhR pathway, which is crucial for regulating intestinal inflammation via IL-22, was evident with both phlorotannin alone and synbiotic administration. The combination of TAs and LC amplified the synergistic effect on intestinal immunity and microbiota, favoring beneficial species and optimizing the Firmicutes/Bacteroidetes ratio. Overall, synbiotic use demonstrated superior preventive effects against UC, suggesting its potential benefits for improving the gut immune system through gut microbiota-derived metabolites.

P336 Exploring Extracellular Matrix Markers in Ulcerative Colitis: Degradation and Formation Insights

Abstract Background The gold standard for assessing disease activity in ulcerative colitis (UC) is endoscopy, which is uncomfortable for the patient, and only evaluates the superficial layers of the colon. Intestinal extracellular matrix (ECM) remodeling is highly dynamic during disease activity and blood spillover of ECM components might reflect transmural disease burden. The aim of this study was to evaluate baseline serum markers of ECM formation (PRO-C11, PRO-C22, and PRO-C7) and degradation (C7M) to assess disease activity and treatment response in UC. Methods Forty-nine UC patients with active disease and 50 healthy controls (HC) were included. All underwent endoscopy and blood sampling at inclusion. UC patients additionally had fecal calprotectin (FCP) measured at baseline and had treatment adjusted at the discretion of the attending physician. Subsequent follow up of UC patients included clinical activity score, FCP, and blood samples at 3 and 6 months as well as an endoscopy at 6 months. Ulcerative Colitis Endoscopic Index of Severity (UCEIS), total Mayo score (TMS), and disease extent (E1-E3) was registered. Response was defined as a reduction from severe to moderate or mild disease based on TMS. If no follow-up endoscopy was performed (n=9), partial Mayo was used. Spearman’s correlation and one-way-ANOVA with Turkey correlation and correction for multiple testing were applied for statistical analysis. Results All markers of ECM degradation and formation were elevated in patients with severely active UC measured by both UCEIS and TMS compared to HC (adjusted p<0.0001 for each marker). CM7 and PRO-C22 differentiated moderate from severe UC by TMS (p<0.0001) and UCEIS (p<0.05) (Figure 1A-B). Baseline C7M, PRO-C7, and PRO-C11 correlated with CRP (Spearman’s: r=0.82, p<0.0001; r=-0.45, p=0.0012; and r=-0.33, p=0.032, respectively). None of the markers correlated with FCP. Elevated C7M, PRO-C7, and PRO-C11 levels for E3 could differentiate E3 from E1 (Difference ng/ml: 3.89 (SE of diff: 1.47), 13.15 (4.55), 10.08 (4.09), respectively, all p<0.05) (Figure 1C-E). Remission was achieved in 18/49 patients at 6 months. Both C7M and PRO-22 exhibited acceptable discriminative capabilities at baseline for 6-month TMS between remission and non-remission (AUC 0.72 (95% CI 0.58-0.87) p=0.01 and AUC 0.68 (95% CI 0.53-0.83) p=0.04, respectively) (Figure 1F-G). Conclusion This study demonstrates that ECM markers correlate with disease activity, disease extent, and predict future disease outcome in UC. ECM markers hold great promise as they provide a 'window' into transmural tissue remodeling and inflammatory and fibrotic burden, warranting further investigation.

P887 Comparative efficacy of JAK inhibitors versus vedolizumab in patients with hypoalbumineamia and Ulcerative colitis

Abstract Background The IBD community are seeking ways to personalize medication choices for individual patients. Hypoalbumineamia is a poor prognostic marker in ulcerative colitis (UC) as a surrogate marker of disease activity. Biologic molecules are intermittently dosed using albumin binding to maintain plasma concentration, therefore in low albumin states drug clearance is accelerated. This effect is potentially less significant in regularly dosed, JAK inhibitors (JAKi). Methods All patients at our unit taking a JAKi were included. Patients using vedolizumab were selected for inclusion based on the nearest neighbour with respect to medication start date. Vedolizumab was chosen as a second line advanced therapy used regularly in UC. Demographic and disease characteristics were collected. Blood tests immediately prior to starting medication were collected. Outcome measure was response to treatment based based on drug continuation and clinician documentation of treatment success at 6 months. Results 56 patients were included; 28 receiving a JAKi, 28 patients using vedolizumab. The JAKi group consisted of 8 patients receiving Filgotinib, 12 Tofacitinib and 8 Upadacitinib. Patients receiving JAKi were younger (mean age 44 years, SD 14) compared to vedolizumab (56 years, SD 20). Both were predominantly white (JAKi n=16, Vedolizumab n=22). Chronic liver disease was uncommon in both groups; JAKi n=2 (7.1%) and vedolizumab n=3 (10.7%), none of whom had cirrhosis. More hospital admissions were observed in the year prior to starting treatment in patients who received JAKi (n=16, 57.1%) compared to vedolizumab (n=9, 32%). Hypoalbuminaemia (defined as ≤30g/L) was seen in 5 patients in each group. In patients receiving JAKi 16/23 (69.7%) patients without hypoalbuminaemia responded to treatment at 6 months, compared to 3/5 (60%) with low albumin. (p=0.999). In patients receiving Vedolizumab 18/23 (78.3%) patients responded to treatment at 6 months, compared to 1/5 (20%), (p=0.026). Conclusion In patients with hypoalbumineamia, vedolizumab was less effective compared to normal albumin states. A similar effect was not observed in patients receiving JAKi. Numerically the efficacy of both vedolizumab and JAKi was worse in patients with hypoalbuminaemia, as would be expected given the likely reflection of increased disease severity. This data suggests that those patients requiring advanced therapy with hypalbuminaemia might respond better to a JAKi. Further research is needed to investigate this finding.

Serum neutrophil gelatinase-associated lipocalin as promising diagnostic marker and a predictor of activity of ulcerative colitis patients: single center study

Objective The study aimed to detect the diagnostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) in ulcerative colitis (UC) patients, and to evaluate the relation between its value and the clinical activity of the disease. Background Inflammatory bowel disease including UC is chronic inflammatory gastrointestinal disease characterized by remissions and exacerbations and needs invasive diagnosis. Serum NGAL is type of protein its expression is increased in inflamed intestine, and released from activated neutrophils. Patients and methods The study was performed on 75 patients with UC diagnosed by laboratory investigations including erythrocyte sedimentation rate, C-reactive protein, and complete blood count, lower endoscopy, histopathological examination, and activity according to Mayo score was recorded. Also 30 healthy control age sex matched, both groups subjected to measurement of serum NGAL. Results There was highly significant elevation of serum NGAL in UC patients compared with healthy control with P value less than 0.001, moreover serum NGAL was positively correlated with clinical activity of the disease as recorded by Mayo score. The study show cut off value of NGAL more than 74 ng/ml with sensitivity 96% and specificity 66.7%. Conclusion Serum NGAL can be used as noninvasive diagnostic marker of UC and corresponds to clinical and endoscopic activity of the disease.

Is the Mediterranean Diet in Inflammatory Bowel Diseases Ready for Prime Time?

The rising incidence of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), specifically in the developing world, suggests an important environmental effect. Amongst environmental influences, dietary factors, particularly the adoption of a westernized diet, have been specifically noticed. In contrast, the Mediterranean diet (MED), characterized by high intake of fruits, vegetables, whole grains, legumes, nuts, olive oil, and moderate consumption of animal and ultra processed foods, has shown potential positive effects in IBD. Here we conducted a narrative review focusing on the evidence regarding the role of MED in IBD prevention and management. Epidemiological studies suggest inverse association of MED with CD development. Furthermore, adherence to MED has been associated with clinical improvement in active CD and maintenance of lower levels of inflammatory markers in UC, along with improved quality of life and lower mortality rates in IBD patients. Mechanistically, MED promotes a diverse and beneficial gut microbiota, possesses anti-inflammatory properties through polyphenols and dietary fats, and may modulate oxidative stress. In clinical practice, MED may be adapted to diverse disease phenotypes and cultural preferences, and is a sustainable, easy to maintain dietary approach. Current evidence may support the integration of MED into clinical practice in IBD care. In future research, the efficacy of MED in specific IBD phenotypes should be assessed.

Serum Bile Acid Metabolites Predict the Therapeutic Effect of Mesalazine in Patients with Ulcerative Colitis.

Ulcerative colitis (UC) is a systematic chronic disease characterized by insufficient intestinal absorption, and mesalazine is a common medical treatment. In the present study, 20 normal healthy controls (NC group), 10 unmedicated UC patients (UC group), and 20 mesalazine-responsive and 20 mesalazine-nonresponsive UC patients were recruited. A total of 42 serum BA metabolites, including 8 primary bile acids and 34 secondary bile acids (SBAs), were quantitatively measured. Compared with the NC group, serum SBAs in the UC patients were significantly lower but increased after mesalazine therapy. Differences in the serum TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S metabolites were found between the UC and NC groups, with AUC values of 0.777, 0.800, 0.815, 0.775, and 0.740, respectively. Furthermore, we identified 12-keto LCA as a specific BA marker of UC and BA biomarkers of mesalazine responsiveness. It was concluded that serum SBAs were decreased in UC patients, and TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S might aid in the diagnosis of UC. The abundance of SBAs increased after the mesalazine therapy, and serum 12-keto LCA was identified as an alternative invasive biomarker associated with UC diagnosis and therapeutic response, thereby providing a new approach for the prediction of response to mesalazine therapy in UC patients.

Neutrophil-to-lymphocyte ratio may predict clinical relapse in ulcerative colitis patients with mucosal healing.

Endoscopic mucosal healing (MH) is an important treatment goal for patients with ulcerative colitis (UC). The neutrophil-to-lymphocyte ratio (NLR) reflects systemic inflammation and has been reported to be a useful predictive marker for UC. This study aimed to evaluate the clinical utility of the NLR for predicting clinical relapse in UC patients with MH. We retrospectively enrolled patients with UC who underwent colonoscopy at the Osaka City University Hospital between January 2010 and December 2010, whose Mayo Endoscopic Subscore was 0 or 1. The correlation between the incidence of relapse and demographic factors, including the NLR, was analyzed. We included 129 patients in the present study. The median NLR at the time of endoscopy was 1.98, and differences in the high NLR group and the low NLR group were compared. During a median follow-up period of 46.4 months, 58 patients (45.0%) experienced relapse. The cumulative relapse-free rate was significantly higher in the low NLR group than in the high NLR group (P = 0.03, log-rank test). Multivariate analysis identified high NLR as an independent prognostic factor for clinical relapse (hazard ratio, 1.74; 95% confidence interval, 1.02-2.98; P = 0.04). NLR is a novel and useful predictor of clinical relapse in UC patients with MH, and it can potentially be a strong indicator to determine the appropriate treatment strategy and decision-making in clinical practice.

Fecal Calprotectin as a Disease Activity and Prognostic Marker in Ulcerative Colitis

Fecal Calprotectin as a Disease Activity and Prognostic Marker in Ulcerative Colitis

Anti–Integrin αvβ6 Antibody as a Diagnostic Marker for Pediatric Patients With Ulcerative Colitis

Anti–Integrin αvβ6 Antibody as a Diagnostic Marker for Pediatric Patients With Ulcerative Colitis

Assessment of inflammatory markers in ulcerative colitis and association with the disease

Assessment of inflammatory markers in ulcerative colitis and association with the disease

Can ischemia modified albumin level be regarded as an indicative marker of ulcerative colitis and its activity?

Can ischemia modified albumin level be regarded as an indicative marker of ulcerative colitis and its activity?

Integrative analysis of ferroptosis-related genes in ulcerative colitis.

ObjectiveThe aim of this study was to identify and validate ferroptosis-related markers in ulcerative colitis (UC) to explore new directions for UC diagnosis and treatment.MethodsWe screened UC chips and ferroptosis-related genes from the Gene Expression Omnibus (GEO), FerrDb, and GeneCards databases. The differentially expressed genes (DEGs) and ferroptosis-related DEGs between the UC group and normal controls were analyzed using bioinformatics methods. Enrichment analysis, protein–protein interaction analysis, and hub genes were screened. Peripheral blood chip and animal experiments were used to validate the ferroptosis-related hub genes. Finally, hub gene–transcription factor, hub gene–microRNA (miRNA), and hub gene–drug interaction networks were constructed.ResultsOverall, 26 ferroptosis-related DEGs were identified that were significantly enriched in energy pathways and metabolism. We identified ten ferroptosis-related hub genes from the protein–protein interaction network: IL6, PTGS2, HIF1A, CD44, MUC1, CAV1, NOS2, CXCL2, SCD, and ACSL4. In the peripheral blood chip GSE94648, CD44 and MUC1 were upregulated, which was consistent with the expression trend in GSE75214. Animal experiments showed that CD44 expression was significantly increased in the colon.ConclusionsOur findings indicate that CD44 and MUC1 may be ferroptosis-related markers in UC.

MiRNA-Based Potential Biomarkers and New Molecular Insights in Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease, which usually manifests as abdominal pain, diarrhea and hematochezia. The disease often recurs and is difficult to cure. At present, the pathogenesis is not clear, but it is believed that the disease is caused by a complex interaction among immunity, heredity, environment and intestinal microflora disorders. MicroRNA (miRNA) is endogenous single-stranded non-coding RNA of 17–25 nucleotides (nts). They target the 3'Untranslated Region of a target gene and inhibit or degrade the target gene according to the extent of complementary bases. As important gene expression regulators, miRNAs are involved in regulating the expression of most human genes, and play an important role in the pathogenesis of many autoimmune diseases including UC. Studies in recent years have illustrated that abnormal expression of miRNA occurs very early in disease pathogenesis. Moreover, this abnormal expression is highly related to disease activity of UC and colitis-associated cancer, and involves virtually all key UC-related mechanisms, such as immunity and intestinal microbiota dysregulation. Recently, it was discovered that miRNA is highly stable outside the cell in the form of microvesicles, exosomes or apoptotic vesicles, which raises the possibility that miRNA may serve as a novel diagnostic marker for UC. In this review, we summarize the biosynthetic pathway and the function of miRNA, and summarize the usefulness of miRNA for diagnosis, monitoring and prognosis of UC. Then, we described four types of miRNAs involved in regulating the mechanisms of UC occurrence and development: 1) miRNAs are involved in regulating immune cells; 2) affect the intestinal epithelial cells barrier; 3) regulate the homeostasis between gut microbiota and the host; and 4) participate in the formation of tumor in UC. Altogether, we aim to emphasize the close relationship between miRNA and UC as well as to propose that the field has value for developing potential biomarkers as well as therapeutic targets for UC.

Evaluation of Serum Leucine-Rich Alpha-2 Glycoprotein as a New Inflammatory Biomarker of Inflammatory Bowel Disease.

Studies on serum leucine-rich alpha-2 glycoprotein (LRG) in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are scarce; the methods for estimating disease activity are less established, particularly for CD. This study is aimed at evaluating the utility of serum LRG as a potential inflammatory marker for IBD and to investigate the LRG gene expression in peripheral blood mononuclear cells (PBMCs) as a possible source of serum LRG. Overall, 98 patients with UC and 96 patients with CD were prospectively enrolled and clinically evaluated; 92 age-matched individuals served as the healthy controls. The blood samples were analyzed for serum LRG levels and routine laboratory parameters. Disease activity was assessed clinically and endoscopically. Finally, LRG gene expression in the PBMCs from a different cohort (41 patients with UC, 34 patients with CD, and 30 healthy controls) was examined. The serum LRG levels were higher during active disease than during inactive disease; additionally, serum LRG levels were positively correlated with clinical disease activity, C-reactive protein (CRP) levels, and other laboratory parameters in patients with UC and CD and with endoscopic disease activity in UC. UC and CD showed comparable areas under the curve (AUC) values for determining clinical remission and differentiating between endoscopic remission associated with LRG and CRP. The levels of LRG mRNA were also increased in PBMCs from patients with UC and CD and reflected disease activity. These data suggest that serum LRG, originated partially from PBMCs, is an inflammatory marker in UC and CD. A large-scale well-designed study should be conducted in the future to more accurately reveal the clinical significance of LRG in patients with IBD.

Neutrophil extracellular traps-associated protein peptidyl arginine deaminase 4 immunohistochemical expression in ulcerative colitis and its association with the prognostic predictors

Neutrophil extracellular traps (NETs) are incriminated in several immune and inflammatory diseases including ulcerative colitis (UC). Analysis of colonic tissues for NETs-related markers in UC carries prognostic and therapeutic implications. This work aims to evaluate the immunohistochemical (IHC) expression of NETs-associated-protein arginine deaminase 4 (PAD4) in colonic biopsies from UC patients in comparison to normal colon (NC). Association between PAD4 expression level and histopathologic grade, patient’s therapeutic response and other clinicopathological prognostic predictors in UC are determined. This cohort study included biopsies from 42 UC patients and 11 NC controls. Clinicopathological data including patient's age at diagnosis, gender, presenting symptoms, anatomical disease extent, extra-intestinal manifestations, type and response to therapy and surgical interventions were recorded and tabulated. Histopathological grading of disease activity and associated epithelial changes were assessed. PAD4 immunostaining was conducted using Horseradish Peroxidase technique and scored semiquantitatively considering intensity and percentage of nuclear staining of lamina propria inflammatory cells. Appropriate statistical tests were applied. Anti-PAD4 was localized mainly in the nuclei of lamina propria infiltrating neutrophils. It was expressed more significantly in UC (95.2 %) compared to NC (p 0.001). Increased PAD4 expression level was significantly associated with increasing histopathologic grade, anatomical disease extent, lacking response to therapy and subjection to radical surgery (p:0.001, = 0.038, 0.046, 0.046 respectively). Age, gender, presenting symptoms, extra-intestinal manifestations and epithelial changes showed insignificant associations. This study characterizes a subset of UC patients with high histopathological grade of activity, pancolonic involvement, strong/moderate PAD4 expression levels and who are unresponsive to routine medical therapeutic regimens rendering them candidates for radical surgery. In conjunction with histopathological grading, IHC evaluation of PAD4 in UC is recommended to guide patient’s selection for targeted therapy using the novel-discovered selective PAD4 inhibitors.

An Inverse Correlation of Serum Fibroblast Growth Factor 19 with Abdominal Pain and Inflammatory Markers in Patients with Ulcerative Colitis.

Background and Aims Bile acids (BA) play an important role in the modulation of numerous gut functions. Fibroblast growth factor 19 (FGF19) is the ileal hormone regulating BA homeostasis. The aim of the study was to evaluate serum FGF19 level and its correlation with clinical and endoscopic disease activity indices along with inflammatory biomarkers including serum CRP and fecal calprotectin levels in patients with ulcerative colitis (UC). Methods Fasting serum FGF19 level was measured using ELISA test in 16 patients with active UC (7 F, 9 M), 15 patients with nonactive UC (8 F, 7 M), and 19 healthy controls (11 F, 8 M). The disease activity was assessed based on the clinical and endoscopic evaluations as well as serum CRP and fecal calprotectin level measurement. Results The median serum FGF19 level was higher in patients with nonactive UC (175.3 pg/ml (108.7-342.3)) than in patients with active UC (114.3 pg/ml (68.9-155.3), p = 0.093). The median FGF19 level in healthy controls amounted to 151.6 pg/ml (90.6-224.2), and there were no statistically significant differences between the patients with active and nonactive UC compared to the healthy controls. An inverse correlation was observed between FGF19 level and abdominal pain intensity (R = –0.48, p = 0.007) as well as fecal calprotectin (R = –0.38, p = 0.036) and CRP levels (R = –0.36, p = 0.045). The serum FGF19 level was not correlated neither with clinical nor endoscopic disease activity indices. Conclusions The inverse correlations between FGF19 level and abdominal pain as well as inflammatory markers in UC may imply its potential analgesic and anti-inflammatory effects.

Are Serum-Based Markers Going to Replace Faecal Neutrophil Markers in Ulcerative Colitis?

Are Serum-Based Markers Going to Replace Faecal Neutrophil Markers in Ulcerative Colitis?

PTPRO exaggerates inflammation in ulcerative colitis through TLR4/NF-κB pathway.

Previous studies have implicated protein tyrosine phosphatase receptor type O (PTPRO) as a key regulator in inflammation-associated diseases; however, its role in ulcerative colitis (UC) remains largely unknown. Thus, we aim to elucidate the potential role and underlying mechanism of PTPRO in UC. In this study, increased expression of PTPRO, toll-like receptor (TLR4) and inflammatory cytokines were observed in mucosal tissues (MTs) from inflamed areas and lamina propria mononuclear cells (LPMCs) of patients with UC compared with those from healthy controls. Then, it was manifested that PTPRO promoted the expression of TLR4 and proinflammatory cytokines in lipopolysaccharide-induced (LPS-induced) inflammatory macrophage model. Besides, PTPRO inhibited the proliferation of intestinal epithelial cells (IECs) but enhanced the apoptosis of IECs in macrophages. Moreover, levels of phosphorylated nuclear factor κB (NF-κB)/p65 and inhibitor of NF-κB α (IκBα) were more significantly increased in PTPRO overexpressed macrophages. In addition, the area under receiver operating characteristic curve was 0.807 (95%CI = 0.686-0.958, P < .001) suggesting PTPRO as an ideal diagnostic marker for UC. Taken these, the present study shows strong evidence that PTPRO exaggerates inflammation in UC via TLR4/NF-κB signaling pathway.

Nonenzymatic Serum Antioxidant Capacity in IBD and Its Association with the Severity of Bowel Inflammation and Corticosteroids Treatment.

Background and objectives: Oxidative stress signalling plays a monumental role in inflammatory bowel disease (IBD). Reduction of oxidative stress might control inflammation, block tissue damage, and reverse natural history of IBD. We assessed the serum concentrations of free thiols (FT) and uric acid (SUA), together constituting a large part of nonenzymatic serum antioxidant capacity, as well as total antioxidant status (TAS) with reference to IBD phenotype, activity, co-occurrence of anemia, and treatment with azathioprine (AZA) and corticosteroids (CS). Additionally, we appraised the potential of uric acid, thiol stress, and TAS as mucosal healing (MH) markers in ulcerative colitis. Materials and methods: SUA, FT, and TAS were measured colorimetrically using, respectively, uricase, Ellman’s and 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) methods. Results: The study group consisted of 175 individuals: 57 controls, 71 ulcerative colitis (UC), and 47 Crohn’s disease (CD) patients. When compared to controls, SUA levels were significantly lower in patients with CD, and FT and TAS levels were significantly lower in patients with CD and UC. In UC patients, SUA, FT, and TAS inversely correlated with the severity of bowel inflammation. As MH markers, SUA displayed better overall accuracy and higher specificity than FT. In active CD, FT, and SUA were significantly lower in patients with anemia. FT was significantly lower in patients treated with corticosteroids. Conclusions: IBD patients, regardless the disease phenotype, have systemic thiol stress, depleted total antioxidant capacity, and reduced concentrations of uric acid, reflecting, to various degrees, clinical and local disease activity as well as presence of anaemia, the most common extraintestinal manifestation of IBD. Evaluation of systemic total antioxidant status may be useful in noninvasive assessment of mucosal healing. Our findings on thiol stress provide an additional aspect on adverse effects of corticosteroids therapy.

TGF-Β as a Marker of Ulcerative Colitis and Disease Severity

Abstract Ulcerative colitis (UC) represents chronic inflammation of the large intestine. Immune response plays an important role in disease genesis and progression. Activated leukocytes secrete several cytokines that actively regulate the inflammatory response in UC. The aim of this study was to determine levels of cytokines IL-17, IL-27, IFN-γ and TGF-β in patients with UC and to test them as biomarkers for disease. The blood samples of 24 patients with ulcerative colitis without previous treatment and 37 healthy individuals were analyzed. Serum levels of IL-17, IL-27, IFN-γ and TGF-β were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Serum levels of IL-17, IL-27, IFN-γ and TGF-β were increased in patients with UC, compared to healthy controls (p=0.022; p=0.001; p=0.001; and p=0.002; respectively). Ratios of cytokines IL-27/IL-17, IFN-γ/TGF-β and IL-17/TGF-β were significantly higher in group of patients with UC (p=0.002; p=0.002; p=0.003; respectively). Serum value of TGF-β higher than 20 pg/ml presents a highly sensitive and specific marker for UC. We believe that increased production and predominance of immunosupressive TGF-β may represent compensatory mechanism for ongoing pro-inflammatory processes in UC.