Plasma thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 levels in inflammatory bowel disease

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an increased risk of thromboembolic events. Imbalance of fibrinolysis has been suggested as one of the possible pathogenetic mechanisms. As plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) are inhibitors of fibrinolysis, we studied TAFI as well as PAI-1 plasma levels in IBD patients compared with healthy controls. METHODS: A total of 132 IBD patients [68 ulcerative colitis (UC) and 64 Crohn's disease (CD)] and 50 healthy controls were enrolled. PAI-1 and TAFI plasma levels were assessed by commercially available enzyme-linked immunosorbent assay kits. Their relationship with clinical parameters of UC and CD was assessed. RESULTS: Mean plasma PAI-1 levels were significantly higher in both UC patients (3.9+/-1.3 IU/ml) and CD patients (4.0+/-1.5 IU/ml) compared with healthy controls (3.1+/-1.1 IU/ml) (P=0.01). On the other hand, mean plasma TAFI levels were significantly lower in both UC patients (14.7+/-3.1 microg/ml) and CD patients (13.3+/-3.4 microg/ml) compared with healthy controls (17.4+/-3.0 microg/ml) (P<0.0001). Patients with active disease had significantly higher PAI-1 levels compared with patients with inactive disease for both diseases (P=0.03 and P=0.01, respectively). No significant association between plasma TAFI levels and disease activity was also found. Plasma TAFI levels were significantly lower in patients with ileal CD compared with patients with colonic CD. CONCLUSION: PAI-1 plasma levels are increased whereas TAFI levels are decreased in IBD patients. These results suggest an imbalance of fibrinolysis in IBD.     

TWEAK is not elevated in patients with newly diagnosed inflammatory bowel disease

Objective: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) may be involved in the pathogenesis of inflammatory bowel disease. The aim was to investigate if TWEAK may reflect disease activity in inflammatory bowel disease.

Materials and methods: In this cohort study, 139 consecutive patients with newly diagnosed and previously untreated inflammatory bowel disease – 95 with ulcerative colitis (UC) and 44 with Crohn’s disease (CD) – underwent colonoscopy. Disease activity was assessed by the Mayo score and the Mayo endoscopic score (MES) for UC, or the Simple Endoscopic Score (SES) for CD. Serum C-reactive protein (CRP) and fecal calprotectin were measured in IBD patients, as were plasma TWEAK levels in patients and 85 healthy subjects. Associations between TWEAK levels and disease activity markers were explored.

Results: In the total IBD group, the median (interquartile range) TWEAK level was 430?pg/ml (109–6570), in UC 502?pg/ml (109–4547) and in CD patients 352?pg/ml (101–9179), respectively. Healthy subjects had a median (IQR) TWEAK of 307?pg/ml (63–3492). There were no significant differences in TWEAK levels between the total IBD group and healthy control subjects, nor between UC and CD, or between UC/CD and healthy subjects. Furthermore, we found no significant associations between Mayo scores, MES-UC, SES-CD, CRP, and fecal calprotectin with plasma TWEAK levels.

Conclusions: Plasma TWEAK levels do not reflect disease activity or the grade of inflammation in patients with newly diagnosed inflammatory bowel disease. NCT01551563.     

Saliva Interleukin-6 in patients with inflammatory bowel disease

Objective. The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions that affect the gastrointestinal tract. In regulation of this inflammatory process, Interleukin-6 (IL-6) has a major role. Overproduction of IL-6 by immunocompetent cells contributes to development of the inflammatory condition. Elevated levels of IL-6 in saliva could be expected, because the saliva-producing cells are part of the digestive system. Material and methods. IL-6 concentrations in saliva and plasma were studied in patients with CD (n=15), UC (n=7) and reference persons (RP) (n=19) by use of an ELISA method. Results. A significant difference in saliva IL-6 concentration between CD patients (median 16.9 ng/L; p<0.05) and RP (median 6.3 ng/L) was found. A significant difference in plasma IL-6 concentration between CD (median 10.3 ng/L; p<0.001) or UC (median 7.8 ng/L; p<0.001) and RP (median 0.8 ng/L) was observed. In patients with CD, plasma IL-6 correlated significantly with C-reactive protein (CRP) as well as albumin. In patients with UC, saliva IL-6 and plasma IL-6 correlated significantly with AI (activity index) scores as well as albumin. In patients with UC, a significant correlation between the saliva and plasma IL-6 concentrations was found. Conclusions. IL-6 was found in saliva in patients with IBD, documenting the general involvement of the gastrointestinal tract extending to the mouth cavity, and measuring IL-6 may be an additional method for evaluating and monitoring the disease activity.     

Differential behavior of coagulation factor XIII in patients with inflammatory bowel disease and in patients with giant cell arteritis

The aim of this prospective study was to examine the role of coagulation factor XIII (FXIII) in relation to disease activity in inflammatory bowel disease (IBD) and in giant cell arteritis. Plasma FXIII activity was studied during active and inactive disease in newly diagnosed patients with Crohn's disease (CD; n = 20), ulcerative colitis (UC; n = 18) and giant cell arteritis (GCA; n = 19), in 3-month intervals (median follow-up 12 months). FXIII was also measured in two noninflammatory control groups, age and sex matched for IBD (n = 25) and GCA (n = 26). FXIII activity was significantly lower in active CD or UC than in active GCA or the noninflammatory controls. Both in CD and UC, FXIII activity correlated inversely with indices of clinical disease activity, the erythrocyte sedimentation rate, fibrinogen and C-reactive protein levels. Low FXIII activity is a characteristic feature of active IBD, and serial measurements may be useful to assess IBD activity.     

Assessment of thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels in inflammatory bowel diseases

OBJECTIVES: Hypofibrinolysis has been proposed as a possible mechanism underlying the known risk of thrombosis observed in patients with inflammatory bowel diseases (IBD). Thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently described inhibitor of fibrinolysis. Increased TAFI plasma levels are associated with a risk for venous thrombosis. The objective was to evaluate TAFI plasma levels and their possible correlations with clinical features and acute-phase reactants in IBD patients. METHODS: Eighty-one IBD patients (47 Crohn's disease and 34 ulcerative colitis) and 81 sex- and age-matched healthy controls were enrolled in the study; moreover, we studied 30 inflammatory controls (13 Reiter's syndrome, 4 Beh?et's syndrome, and 13 patients with newly diagnosed celiac disease). TAFI plasma levels were assessed by means of a commercially available ELISA kit. Erythrocytes sedimentation rate, C-reactive protein, and alpha1-acid glycoprotein were measured as acute-phase reactants. Statistical analysis was performed by means of nonparametric tests and Fisher's exact test and chi(2) test for independence. RESULTS: Median TAFI plasma levels were significantly higher in IBD patients (116.0%, range: 39.0-232.0%) and in inflammatory controls (176.0%, 50.0-435.0%) than in healthy controls (99.0%, 40.0-170.0%) (p< or = 0.05 and p< or = 0.001, respectively). TAFI plasma levels higher than the 95th percentile of control values were significantly more frequent in IBD patients (19.7%) and in inflammatory controls (53.3%) than in healthy controls (4.9%) (p< or = 0.008 and p< or = 0.0001, respectively) and more frequent in clinically active IBD than in clinically quiescent IBD (31.4%vs 10.9%, p< or = 0.03). Finally, in IBD, significant correlations were observed between TAFI plasma levels and erythrocytes sedimentation rate (p< or = 0.02), C-reactive protein (p< or = 0.001), and alpha1-acid glycoprotein (p< or = 0.05). CONCLUSIONS: TAFI plasma levels are increased in IBD patients and correlate with acute-phase reactants. Increased TAFI plasma levels might contribute to the prothrombotic state observed in IBD through the induction of hypofibrinolysis.     

Long non-coding RNA ANRIL serves as a potential marker of disease risk,inflammation, and disease activity of pediatric inflammatory bowel disease

BackgroundLong non-coding antisense RNAs in the INK4 locus (lnc-ANRIL) have been reported to be involved in inflammation and immunity. However, few studies have reported its clinical application in pediatric inflammatory bowel disease (IBD). Therefore, we conducted this study to investigate the correlation between lnc-ANRIL expression and disease risk, inflammation, and activity in pediatric IBD patients.MethodsPediatric patients with Crohn's disease (CD; n = 40), ulcerative colitis (UC; n = 40), and controls (n = 20) were recruited. For all pediatric IBD patients, lnc-ANRIL expression in peripheral blood mononuclear cells and serum inflammatory cytokine levels were measured by RT-qPCR and ELISA, respectively. For the controls, lnc-ANRIL expression was also measured.ResultsLnc-ANRIL levels were lower in CD (P = 0.002) and UC (P = 0.001) patients compared with the controls; negatively correlated with C-reactive protein levels (P<0.01), erythrocyte sedimentation rate (P<0.01), disease activity (P<0.05), and severity (P<0.05) in CD and UC patients; and inversely associated with tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-17, and IL-23 levels in both CD and UC patients (all P<0.01). Further subgroup analyses revealed that the association between lnc-ANRIL and inflammatory cytokines and disease activity was more remarkable in pediatric patients with moderate or severe IBD.ConclusionLnc-ANRIL may serve as a potential marker for evaluating disease risk and monitoring disease activity in pediatric IBD patients.     

Serum 25-hydroxyvitamin D concentration and inflammatory bowel disease characteristics in Romania

AIM: To describe the relationship between vitamin D levels and inflammatory bowel disease (IBD) characteristics in northeastern Romanian patients.METHODS: This was a prospective study of 47 consecutive IBD patients admitted to The Institute of Gastroenterology and Hepatology in Iasi, Romania between March 2011 and June 2012. The diagnosis of IBD was established based on endoscopic, histologic and radiologic findings. Demographic data, disease characteristics, ongoing treatments and biological parameters of patients (including markers of inflammation: C-reactive protein level, fibrinogen level, and erythrocyte sedimentation rate) were recorded. Serum vitamin D levels were measured and compared with age- and sex-matched healthy volunteers from the same geographic area. Vitamin D levels were defined as sufficient (> 30 ng/mL), insufficient (20-30 ng/mL), or severely deficient (< 20 ng/mL).RESULTS: Thirty-three of the IBD patients included in this study had ulcerative colitis (UC) and 14 had Crohn’s disease (CD). Only 24% of the UC patients and 21% of the CD patients had sufficient vitamin D levels. The vitamin D levels were significantly lower in the CD patients with moderate to severe disease activity compared to the CD patients in remission or with mild disease activity (16 ± 6 ng/mL vs 26 ± 7 ng/mL; 16 ± 6 ng/mL vs 31 ± 9 ng/mL, respectively, P < 0.05). Vitamin D levels in the UC patients were not influenced by disease activity and no correlation was observed with the inflammation markers tested (C-reactive protein, fibrinogen, and erythrocyte sedimentation rate). No association was observed between vitamin D levels and smoking status or ongoing medication (5ASA, steroids, and anti-TNFα). Newly diagnosed IBD patients had lower vitamin D levels than patients with established cases, though these differences were not significant (UC: 22 ± 9 ng/mL vs 26 ± 12 ng/mL; CD: 18 ± 6 ng/mL vs 27 ± 11 ng/mL, respectively). Although no association was found between the season during which the visit was scheduled and vitamin D levels, the UC patients assessed during the winter tended to have lower levels than those assessed during the summer (22 ± 9 ng/mL vs 28 ± 13 ng/mL, respectively).CONCLUSION: Vitamin D levels are significantly reduced in IBD patients in northeastern Romania, with the lowest levels occurring in CD patients with moderate to severe disease activity.     

Accuracy of the highly sensitive C-reactive protein/albumin ratio to determine disease activity in inflammatory bowel disease

Persistent disease activity is associated with a poor prognosis in patients with inflammatory bowel disease (IBD). This study aims to explore the accuracy of the highly sensitive C-reactive protein/albumin ratio (CAR) in determining IBD activity.The clinical data of 231 IBD patients treated at Peking Union Medical College Hospital from 2012 to 2018 were analyzed retrospectively. The patients were classified as having active disease or remission according to the Crohn disease activity index scores for patients with Crohn disease (CD) and partial Mayo scores for patients with ulcerative colitis (UC).This study included 231 IBD patients (137 CD and 94 UC). From these groups, 182 patients had active disease, while 49 patients were in remission. The platelet counts, erythrocyte sedimentation rates, high-sensitivity C-reactive protein levels, and CAR scores were significantly higher, while hemoglobin levels, ALB, and body mass indexes were significantly lower in patients with active disease (P < 0.01). The hsCRP, CAR, and ALB significantly correlated with disease activity for both CD and UC (P < 0.001). The area under the curve (AUC) of CAR was highest among the laboratory indexes at 0.829, and the AUC of CAR in the UC patients was larger than that of the CD patients. Also, CAR with cutoff value of 0.06 displayed the highest sensitivity among the indexes for IBD activity at 83.05%.CAR is a useful biomarker for identifying disease activity in patients with CD and UC. Higher CAR levels are indicative of increased IBD activity. CAR may be more valuable in UC than that in CD for assessing the degree of IBD activity.     

Elevated thrombopoietin serum levels in patients with inflammatory bowel disease

OBJECTIVES: Elevated platelet count is a well recognized marker of inflammatory bowel disease (IBD) activity. Thrombopoietin (TPO) is a critical cytokine in the physiological regulation of thrombopoiesis. The aim of this study was to investigate the serum levels of endogenous TPO in patients with IBD, the relationship between platelet counts and TPO levels, and the correlation of TPO with the clinical characteristics of the patients. METHODS: TPO levels in 40 patients with Crohn's disease (CD), 63 patients with ulcerative colitis (UC), and in 42 healthy blood donors were assessed by ELISA. Platelet and white blood cell counts as well as C-reactive protein, and erythrocyte sedimentation rate were measured. RESULTS: TPO levels were significantly elevated in patients with CD (mean 124.3 +/- SD 58.0 pg/ml, p < 0.0001) and in patients with UC (mean 152.2 +/- SD 142.3 pg/ml, p < 0.0001), compared to controls (mean 53.4 +/- SD 45.7 pg/ml). TPO levels remained significantly elevated in remission (mean 144.7 +/- SD 131.1 pg/ml, p < 0.0001 compared to controls). Platelets were significantly elevated only in active CD, being normal in inactive disease as well as in all patients with UC. There was no significant correlation between TPO levels and various clinical characteristics of patients with IBD. No significant correlation was found between TPO levels and either platelet counts or white blood cell counts, erythrocyte sedimentation rate, and C-reactive protein. CONCLUSIONS: TPO levels are increased in IBD, irrespective of disease activity, platelet counts, and clinical characteristics of the patients. These observations indicate that TPO, apart from being a platelet producer, might have additional functions, probably related to the procoagulant state of IBD.     

炎症性肠病患者血浆TRAF1的表达及其临床意义

目的比较炎症性肠病患者血浆肿瘤坏死因子受体相关因子-1（tumor necrosis factor receptor-assoc iated factor-1,TRAF-1）水平和正常对照者的差异,分析血浆TRAF1水平对炎症性肠病的诊断价值以及与内镜下疾病活动性的相关性。方法共纳入62例克罗恩病患者、64例溃疡性结肠炎患者和56例正常对照者。应用酶联免疫吸附试验（Enzym e-linked immuno-sorbent assay,ELISA）分析炎症性肠病患者和正常对照者血浆中TRAF1蛋白的表达,受试者工作特征曲线（rece iver-operating characteristic,ROC）分析血浆TRAF1水平对克罗恩病和溃疡性结肠炎的诊断价值,应用Pearson相关分析研究血浆TRAF1水平与内镜下疾病活动性的相关性。结果克罗恩病患者（P=0.000）和溃疡性结肠炎患者（P=0.000）血浆TRAF1水平显著高于正常对照者,同时TRAF1对区分克罗恩病患者和正常对照者（P=0.000）以及区分溃疡性结肠炎患者和正常对照者（P=0.000）具有显著的诊断价值。克罗恩病患者血浆TRAF1表达水平和内镜下疾病活动指数呈较低的负相关（r=-0.260,P=0.041）,而溃疡性结肠炎患者血浆TRAF1水平与内镜下疾病活动程度无显著相关性（r=0.029,P=0.821）。结论炎症性肠病患者血浆TRAF1水平增高,血浆TRAF1水平对区分炎症性肠病患者和正常对照者具有诊断价值,但血浆中TRAF1的水平不能反应内镜下疾病活动程度。     

Saliva Interleukin-6 in patients with inflammatory bowel disease

OBJECTIVE: The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions that affect the gastrointestinal tract. In regulation of this inflammatory process, Interleukin-6 (IL-6) has a major role. Overproduction of IL-6 by immunocompetent cells contributes to development of the inflammatory condition. Elevated levels of IL-6 in saliva could be expected, because the saliva-producing cells are part of the digestive system. MATERIAL AND METHODS: IL-6 concentrations in saliva and plasma were studied in patients with CD (n=15), UC (n=7) and reference persons (RP) (n=19) by use of an ELISA method. RESULTS: A significant difference in saliva IL-6 concentration between CD patients (median 16.9 ng/L; p<0.05) and RP (median 6.3 ng/L) was found. A significant difference in plasma IL-6 concentration between CD (median 10.3 ng/L; p<0.001) or UC (median 7.8 ng/L; p<0.001) and RP (median 0.8 ng/L) was observed. In patients with CD, plasma IL-6 correlated significantly with C-reactive protein (CRP) as well as albumin. In patients with UC, saliva IL-6 and plasma IL-6 correlated significantly with AI (activity index) scores as well as albumin. In patients with UC, a significant correlation between the saliva and plasma IL-6 concentrations was found. CONCLUSIONS: IL-6 was found in saliva in patients with IBD, documenting the general involvement of the gastrointestinal tract extending to the mouth cavity, and measuring IL-6 may be an additional method for evaluating and monitoring the disease activity.     

Factors affecting vitamin D deficiency in active inflammatory bowel diseases

BackgroundHypovitaminosis D is prevalent in inflammatory bowel disease (IBD) and may be associated with disease activity.AimThis study evaluated vitamin D (VitD) status in an Italian cohort of IBD patients, not taking VitD supplementation. We investigated risk factors for VitD deficiency and its correlation with disease activity.MethodsVitD levels were measured in 300 consecutive outpatients (42% with Crohn’s Disease (CD) and 58% with ulcerative colitis (UC), 56% male) from a tertiary referral center. Data from the IBD cohort were compared with those of 234 healthy controls, matched by sex, age, and the month in which VitD levels were measured.ResultsThe mean VitD level in IBD patients was significantly lower than in controls (18.9 ng/ml vs. 25 ng/ml, p < 0.001) when accounting for gender, age, and season. VitD deficiency was present in 62% of IBD patients. Risk factors for deficiency were: age <40 and ≥60 years, winter, previous surgery, C-reactive protein (CRP) ≥0.5 mg/dl, and erythrocyte sedimentation rate ≥20 mm/h. In multivariate analysis, VitD levels were negatively influenced by disease location and CRP in UC.ConclusionsAlthough VitD deficiency was more prevalent than expected in healthy controls living in a Mediterranean country not at high risk of hypovitaminosis D, it was more common and severe in IBD patients. This study also found an association between VitD status and disease activity     

Plasma levels of soluble CD40 ligand are elevated in inflammatory bowel diseases

BACKGROUND AND AIMS: CD40/CD40 ligand (CD40L) interaction is important for induction of T cell dependent antibody production and cell-mediated immune responses. Overexpression of CD40/CD40L in the intestinal mucosa is likely to be involved in the pathogenesis of inflammatory bowel disease (IBD). A soluble form of CD40L (sCD40L) exists in the circulation. This study investigated whether plasma levels of sCD40L are higher in patients with IBD than in healthy controls. PATIENTS AND METHODS: Plasma levels of sCD40L were measured in 89 patients with Crohn's disease (CD), 56 patients with ulcerative colitis (UC), 17 patients with infectious diarrhea, and 42 healthy controls, using a specific enzyme-linked immunosorbent assay. RESULTS: In CD patients plasma levels of sCD40L were significantly higher than in healthy controls. Patients with UC and infectious diarrhea had higher sCD40L levels than healthy controls, but the differences were not significant. CD patients with fistulas and/or abscesses (n=38) had significantly higher levels of sCD40L than patients with uncomplicated CD (n=51). Only in patients with uncomplicated CD plasma levels of sCD40L correlated significantly with C-reactive protein and alpha(1)-glycoprotein. In UC patients there was a significant correlation of sCD40L with C-reactive protein. However, there was no significant correlation between plasma sCD40L levels and Crohn's disease activity index or Rachmilewitz score. CONCLUSION: Elevated plasma levels of sCD40L in CD patients supposedly reflect activation of functional CD40L in the intestine and might be a marker of intestinal inflammation.     

Effects of anti–TNF-alpha therapy on hemoglobin levels and anemia in patients with inflammatory bowel disease

BackgroundTumor necrosis factor-α (TNF-α) is involved in inducing inflammatory anemia. The potential effect of anti–TNF-α agents on anemia in inflammatory bowel diseases (IBD) is still unknown.MethodsAnalytical data and disease characteristics from 362 IBD patients [271 CD/91UC) treated with anti-TNF-α drugs were retrospectively collected. Effects on disease activity, blood markers and prevalence of anemia were assessed after 6 and 12 months of therapy.Results29.3% patients presented anemia at baseline, and significantly reduced to 14.4% and 7.8% after 6 and 12 months of therapy, respectively. Mean ± SD Hb levels increased significantly at month 6, and this increase was sustained at 12 months. Serum markers of iron metabolism increased significantly compared to baseline, as disease activity measured by C-reactive protein (CRP) was reduced. All these effects were observed independently for CD and UC, and were independent of iron supplementation during treatment. Anemia at baseline (OR 4.09; 95%CI 1.98–8.45) and elevated CRP (OR 3.45; 95CI 1.29–9.22) were independently associated with risk of persistent anemia, as well as iron replacement during therapy (OR 4.36; 95%CI 2.07–9.16).ConclusionsControlling disease activity with anti-TNF- α therapy significantly and independently associated with resolution of anemia in IBD, with no relevant role for iron replacement therapy.     

凝血和纤溶状态的变化对炎症性肠病疾病活动性的影响

目的评价炎症性肠病患者及正常对照者之间凝血和纤溶状态的差异及其和疾病活动性的关系。方法队列研究271例炎症性肠病患者和正常对照者的凝血和纤溶状态,性别分层分析凝血和纤溶状态的改变和炎症活动性的关系。结果炎症性肠病患者血小板、血小板分布宽度、凝血酶原时间、纤维蛋白原和活化部分凝血活酶时间显著高于正常对照者（P〈0.05）,但平均血小板体积显著低于正常对照组（P〈0.05）。多元回归分析显示纤维蛋白原是男性溃疡性结肠炎患者ESR（β=1.316,P=0.000）和CRP（β=1.233,P=0.015）的线性相关因子;血小板（β=0.436,P=0.037）和凝血酶原时间（β=0.810,P=0.000）是女性克罗恩病患者克罗恩病活动指数的线性相关因子。结论炎症性肠病患者凝血和纤溶状态异常和疾病活动性相关,纤维蛋白原、血小板和凝血酶原时间是炎症活动性的预测因素。     

Resistance to activated protein C and low levels of free protein S in Greek patients with inflammatory bowel disease

OBJECTIVE: Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. A recently identified mechanism for thrombophilia, the poor anticoagulant response to activated protein C, has been suggested as one of the leading risk factors for thrombosis. The aim of this study was to evaluate the frequency of thrombophilic abnormalities, including activated protein C-resistance (APCR), in Greek patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Forty-eight patients with UC, 36 with CD, and 61 matched healthy controls (HC) were studied. Cases with presence of lupus anticoagulant, use of anticoagulants or heparin, and pregnancy were excluded. Disease activity in CD was evaluated by use of the Crohns Disease Activity Index (CDAI) score and in UC by the Truelove-Witts grading system. Plasma levels of protein C, free protein S, antithrombin III (AT-III), activated protein C resistance (APCR), and fibrinogen were determined in IBD patients, as well as in HC. All the cases and controls with abnormal APCR were further studied by genetic testing for the factor V Leiden mutation. RESULTS: Mean fibrinogen levels in UC and CD patients were significantly elevated (p<0.0001), compared with HC. The mean values of free protein S, as well as mean APCR, were significantly lower in UC and CD patients than in the HC (p<0.0001). Seven (five UC and two CD) of 84 IBD patients (8.3%) and three of the HC (4.9%) had the factor V Leiden mutation. No significant difference was observed for the other thrombophilic parameters. Fibrinogen levels and profound free protein S deficiency were found related to disease activity. CONCLUSIONS: Thrombophilic defects are common in Greek patients with IBD and they could interfere either in the disease manifestation or in the thrombotic complications.     

Serum Ghrelin Levels in Inflammatory Bowel Disease with Relation to Disease Activity and Nutritional Status

Ghrelin possesses various biological activities -- it stimulates growth hormone (GH) release, plays a major role in energy metabolism, and is one of the hormones that affects body composition. It also plays a role in modulating immune response and inflammatory processes. In this study we aimed to determine whether serum ghrelin levels had correlation with markers associated with disease activation. We also investigated any probable relationship between serum ghrelin level and nutritional status. Serum levels of ghrelin and its relationship with disease activity and nutritional status were evaluated in 34 patients with ulcerative colitis (UC), 25 patients with Crohn's disease (CD), and 30 healthy controls. Serum ghrelin levels, serum IGF-1 and GH levels, and markers of disease activity (sedimentation, C-reactive protein, and fibrinogen) were measured in all subjects. Body composition and nutritional status was assessed by both direct (by anthropometry) and indirect (by bioimpedance) methods. Serum ghrelin levels were significantly higher in patients with active UC and CD than in those in remission (108 +/- 11 pg/ml vs. 71 +/- 13 pg/ml for UC patients, P < 0.001; 110 +/- 10 pg/ml vs. 75 +/- 15 pg/ml for CD patients, P < 0.001). Circulating ghrelin levels in UC and CD patients were positively correlated with sedimentation, fibrinogen and CRP and was negatively correlated with IGF-1, BMI, TSFT, MAC, fat mass (%), and fat free mass (%). This study demonstrates that patients with active IBD have higher serum ghrelin levels than patients in remission and high levels of circulating ghrelin correlate with the severity of disease and the activity markers. Ghrelin levels in inflammatory bowel disease (IBD) patients show an appositive correlation with IGF-1 and bioelectrical impedance analysis, body composition, and anthropometric assessments. Finally, we arrived at the conclusion that ghrelin level may be important in determination of the activity in IBD patients and evaluation of nutritional status.     

Long-term deep remission during maintenance therapy with biological agents in inflammatory bowel diseases

Abstract

Background and aims: A multicentre, retrospective, non-interventional, patient chart review study was conducted to investigate deep (DR) and histological remission rates during maintenance therapy with biological agents in inflammatory bowel disease (IBD).

Methods: We reviewed clinical, endoscopic, and histological findings, and laboratory markers such as C-reactive protein (CRP) and faecal calprotectin (FC) on average of nine years after the initiation of anti-TNF-therapy. DR was defined as no clinical symptoms (The physicians’ global assessment scores; PGA = 0) with endoscopic remission (the Simple Endoscopic Score for Crohn’s Disease [SES-CD]?≤?2 or Mayo endoscopic subscore ≤1). Histological activity was defined as normal if only architectural alterations without cellularity changes occurred.

Results: Of 117 IBD patients on maintenance therapy, 72 (62%; CD n?=?55 [56%], UC n?=?17 [85%]) patients were in DR. Of patients in DR, 76% were also in histological remission. 77% of patients remained on initiated biological treatment. UC patients achieved DR significantly more often than CD patients (p?=?.016). Both median CRP and FC levels were significantly lower in patients with DR.

Conclusion: Reassuringly, almost two thirds of the IBD patients on maintenance therapy with biological agents maintained DR in the long-term, and more than two thirds of patients in DR achieved also histological remission. CD patients in DR had fewer surgical operations due to CD than patients not achieving DR.     

CD99 refers to the activity of inflammatory bowel disease

Background: Inflammatory bowel disease (IBD), composed of Crohn’s disease (CD) and ulcerative colitis (UC), is an inflammatory autoimmune disease. CD99 has been reported to participate in migration of leukocytes and T cell activation. However, the roles of CD99 in IBD are obscure.

Materials and methods: CD99 expression was examined in peripheral blood mononuclear cells (PBMCs) and inflamed mucosa from IBD patients by qRT-PCR. Serum TNF-α and IL-17A levels were detected by ELISA. Correlations of CD99 expression with TNF-α, IL-17A, Crohn’s disease activity index (CDAI), simple endoscopic score for CD (SES-CD), Mayo index, and Truelove grading were performed by Pearson’s correlation.

Results: CD99 expression was increased in PBMCs and inflamed mucosa from active CD and UC patients, and CD99 expression was also increased in the inflamed mucosa compared with unaffected control from the same patients. Serum TNF-α and IL-17A levels were increased in active CD or UC patients, and positively correlated with CD99 expression in PBMCs (CD: r?=?.402, p?=?.009; r?=?.350, p?=?.025. UC: r?=?.289, p?=?.028; r?=?.322, p?=?.014). Moreover, CD99 expression in inflamed mucosa was correlated with CDAI, SES-CD, Mayo index, and Truelove grading (r?=?.410, p?=?.012; r?=?.341, p?=?.005; r?=?.366, p?=?.002; r?=?.312, p?=?.011).

Conclusion: CD99 expression is increased in patients with active IBD, and positively correlated with disease activity. Therefore, CD99 expression can be used as an index to evaluate the activity of IBD.     

Nutritional status in patients with active inflammatory bowel disease: Prevalence of malnutrition and methods for routine nutritional assessment

Background and aimMalnutrition is a common feature of inflammatory bowel disease (IBD). There are numerous methods for the assessment of nutritional status, but the gold standard has not yet been established. The aims of the study were to estimate the prevalence of undernutrition and to evaluate methods for routine nutritional assessment of active IBD patients.Material and methodsTwenty-three patients with active Crohn disease, 53 patients with active ulcerative colitis and 30 controls were included in the study. The nutritional status was assessed by extensive anthropometric measurements, percentage of weight loss in the past 1–6 months and biochemical markers of nutrition.ResultsAll investigated nutritional parameters were significantly different in IBD patients compared to control subjects, except MCV, tryglicerides and serum total protein level. Serum albumin level and bodymass index (BMI) were the most predictive parameters of malnutrition. According to different assessment methods the prevalence of undernutrition and severe undernutrition in patients with active IBD were 25.0%–69.7% and 1.3%–31.6%, respectively, while in the control subjects no abnormalities have been detected. There was no statistically significant difference of nutritional parameters between UC and CD patients except lower mid-arm muscle circumference in UC group.ConclusionsMalnutrition is common in IBD patients. BMI and serum albumin are simple and convenient methods for the assessment of the nutritional status in IBD patients. Further studies with larger group of patients are necessary to elucidate the prevalence of malnutrition and the most accurate assessment methods in IBD patients.