Increased serum levels of eotaxin in patients with inflammatory bowel disease

BACKGROUND: The CC-chemokines eotaxin and eotaxin-2, produced by epithelial and phagocytic cells, are potent and selective chemoattractants for eosinophils and basophils. The eosinophil is a potent inflammatory cell thought to play an important role in the pathogenesis of inflammatory bowel disease (IBD). In this study we investigated the serum concentrations of eotaxin and eotaxin-2 in patients with Crohn disease and ulcerative colitis. METHODS: Thirty-one patients with Crohn disease, 35 patients with ulcerative colitis and 41 control patients were studied. Eotaxin and eotaxin-2 serum levels were measured with solid phase sandwich enzyme-linked immunosorbent assays. RESULTS: Significantly increased serum eotaxin levels were observed in both patients with Crohn disease (289.4+/-591.5 pg/ml) and ulcerative colitis (207.0+/-243.4 pg/ml) when compared with controls (138.0+/-107.8 pg/ml) (P < 0.01). Moreover, patients with active Crohn disease and ulcerative colitis showed significantly higher serum eotaxin levels than patients with quiescent disease (434.0+/-776.8 pg/ml versus 113.8+/-65.4 pg/ml in Crohn disease and 295.7+/-337.1 versus 121.2+/-91.9 pg/ml in ulcerative colitis, P < 0.05). In contrast, there was no significant difference in eotaxin-2 serum levels among patients with Crohn disease (863.5+/-448.2 pg/ml), ulcerative colitis (1028.3+/-431.4 pg/ml) and controls (981.4+/-539.4 pg/ml). CONCLUSIONS: Eotaxin is significantly increased in serum of patients with active Crohn disease and ulcerative colitis, suggesting that this cytokine may play a role in the pathogenesis of IBD.     

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.     

Increased serum levels of YKL-40 in patients with inflammatory bowel disease

BACKGROUND AND AIMS: Initiation of a fibrotic process has been suggested as part of the intestinal response to chronic inflammation in inflammatory bowel disease. YKL-40 has been proposed as a new serum marker of fibrosis. We studied compared the serum levels of YKL-40 in patients with ulcerative colitis or Crohn's disease with inflammatory and healthy controls. PATIENTS AND METHODS: YKL-40 serum levels were measured in 179 patients with inflammatory bowel disease (94 ulcerative colitis, 85 Crohn's disease), in 23 with intestinal inflammation of other causes, and 70 matched healthy controls using a commercially available enzyme-linked immunosorbent assay. YKL-40 levels were assessed in terms of disease activity, type and localization. RESULTS: Mean serum YKL-40 levels were 102.6+/-82.7 ng/ml in ulcerative colitis patients and 112.2+/-83.7 ng/ml in Crohn's disease patients, significantly higher than in healthy controls (64.1+/-21.4 ng/ml) but not significantly different from inflammatory controls (77.8+/-23.1 ng/ml). Disease activity and C-reactive protein levels were significantly correlated with YKL-40 levels in both ulcerative colitis and Crohn's disease. Crohn's disease patients with ileum localization had significantly higher YKL-40 levels than those with ileocolonic or colonic disease. Patients with stenotic disease had mean YKL-40 levels not significantly different than those with nonstenotic disease. CONCLUSION: Serum levels of YKL-40 are increased in patients with inflammatory bowel disease, and this is associated with the inflammatory process rather than with the degree of fibrosis.     

Elevated circulating platelet-derived microparticles in patients with active inflammatory bowel disease

OBJECTIVES: Platelet-derived microparticles (PDMPs) are active molecules involved in the hemostatic and inflammatory responses. To evaluate the changes in the platelet function in patients with inflammatory bowel disease (IBD), we measured circulating PDMP levels. METHODS: Twenty-five healthy controls, 44 patients with ulcerative colitis (UC), and 43 patients with Crohn's Disease (CD) were studied. The PDMP and soluble P-selectin (sP-selectin) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: In the healthy controls, the PDMP levels were 17.2 +/- 6.2 U/mL. Significant differences were not observed between the healthy controls and inactive UC patients (20.8 +/- 9.5 U/mL, n = 25) or between the healthy controls and inactive CD patients (17.6 +/- 7.8 U/mL, n = 24). In contrast, the PDMP levels were significantly higher in both active UC (49.2 +/- 33.6 U/mL, n = 19) and active CD (48.6 +/- 42.8 U/mL, n = 19) patients than in the healthy controls. A significant correlation was found between the PDMP levels and the clinical activity indexes (CAI) of UC patients (r = 0.65, p < 0.01, n = 44), and between the PDMP levels and Crohn's disease activity indexes (CDAI) (r = 0.72, p < 0.01, n = 43). Elevated PDMP levels in active patients were significantly reduced after remission. A significant correlation was observed between the PDMP levels and the sP-selectin levels (r = 0.60, p < 0.01, n = 122). CONCLUSION: Elevated circulating PDMPs in active IBD patients suggest a role for platelets in the pathogenesis of IBD.     

Serum gastrin levels in patients with inflammatory bowel disease

The aim of this study was to estimate the levels of serum gastrin in a group of patients with either ulcerative colitis or Crohn's disease and to compare the results with those of a group of normal controls. In 108 consecutive patients with IBD (66 with ulcerative colitis, 32 with Crohn's disease and 10 with indetermined colitis) serum levels of gastrin were measured by radioimmunoassay. One hundred and eight normal people were served as controls. The levels of serum gastrin were significantly elevated in patients with Crohn's disease compared to normal controls (74.4 +/- 43.9 pg/ml vs. 47.5 +/- 32.4 pg/ml, P<0.05), irrespectively of the activity of the disease. On the contrary, patients with ulcerative colitis exhibited no significant differences compared to normal controls. Differences between Crohn's disease and ulcerative colitis patients were statistically significant (P<0.001). The rate of infection by Helicobacter pylori in patients with inflammatory bowel disease was statistically significantly lower as compared with normal controls (31.7% vs. 55.1%, P<0.001). It is concluded that patients with active or inactive Crohn's disease have increased levels of serum gastrin. This may have implications concerning the high incidence of upper GI lesions found in patients with Crohn's disease despite the very low incidence of Helicobacter pylori infection.     

Urotensin II levels in patients with inflammatory bowel disease

BACKGROUNDPatients with inflammatory bowel disease (IBD) are associated with increased cardiovascular risk and have increased overall cardiovascular burden. On the other hand, urotensin II (UII) is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well. Furthermore, patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls. Since the features of IBD includes chronic inflammation and endothelial dysfunction as well, it is plausible to assume that there is connection between increased cardiac risk in IBD and UII.AIMTo determine serum UII levels in patients with IBD and to compare them to control subjects, as well as investigate possible associations with relevant clinical and biochemical parameters.METHODSThis cross sectional study consecutively enrolled 50 adult IBD patients (26 with Crohn’s disease and 24 with ulcerative colitis) and 50 age and gender matched controls. Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines. Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn’s Disease were used for endoscopic evaluation. Serum levels of UII were determined using the enzyme immunoassay kit for human UII, according to the manufacturer’s instructions.RESULTSIBD patients have significantly higher concentrations of UII when compared to control subjects (7.57 ± 1.41 vs 1.98 ± 0.69 ng/mL, P < 0.001), while there were no significant differences between Crohn’s disease and ulcerative colitis patients (7.49 ± 1.42 vs 7.65 ± 1.41 ng/mL, P = 0.689). There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels (r = 0.491, P < 0.001) and a significant negative correlation between serum UII levels and total proteins (r = -0.306, P = 0.032). Additionally, there was a significant positive correlation between serum UII levels with both systolic (r = 0.387, P = 0.005) and diastolic (r = 0.352, P = 0.012) blood pressure. Moreover, serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity (r = 0.425, P = 0.048) and Simple Endoscopic Score for Crohn’s Disease (r = 0.466, P = 0.028) scores. Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide (β ± standard error, 0.262 ± 0.076, P < 0.001) and systolic blood pressure (0.040 ± 0.017, P = 0.030).CONCLUSIONIt is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients, and its purpose should be investigated in further studies.     

Thrombopoietin serum levels in patients with inflammatory bowel disease with and without previous thromboembolic events

BACKGROUND/AIMS: Patients affected by inflammatory bowel disease frequently suffer from thromboembolic complications and mesenteric microvascular occlusion could be involved in the pathogenesis of inflammatory bowel disease. Increased platelet counts and abnormal platelet function seem to play a crucial role in determining the hypercoagulable state observed in inflammatory bowel disease. Thrombopoietin is considered the primary regulator of thrombopoiesis and recent studies have investigated the role of thrombopoietin in inflammatory bowel disease. However, the available data are not conclusive. The aim of this study was to assess thrombopoietin serum levels in inflammatory bowel disease patients according to platelet counts, disease activity and previous thrombotic events. METHODOLOGY: Seventy-one patients with inflammatory bowel disease [41 with ulcerative colitis and 30 with Crohn's disease] and 30 healthy controls were investigated. Eight (11%) inflammatory bowel disease patients had suffered previous thromboembolic complications, none had active thrombosis. Thrombopoietin serum levels were measured by ELISA. RESULTS: Mean thrombopoietin levels were significantly increased in inflammatory bowel disease patients with active disease compared to both healthy controls and patients with inactive disease. Platelet counts were significantly higher only in patients with active disease with respect to healthy subjects. No correlation was found between thrombopoietin levels and platelet counts in either controls or inflammatory bowel disease patients. No differences were found either in thrombopoietin levels or in platelet counts comparing inflammatory bowel disease patients with and without thromboembolic complications. CONCLUSIONS: Our data show elevated thrombopoietin levels in active inflammatory bowel disease. However, no correlation was found between platelet counts and thrombopoietin levels, supporting the hypothesis that other circulating factors than thrombopoietin interact in determining reactive thrombocytosis. Furthermore, thrombopoietin levels did not differ in inflammatory bowel disease patients with or without previous thromboembolic events. This finding could be probably explained by the lack of patients with active thrombosis at the moment of inclusion in the study.     

Elevated plasma cryofibrinogen in patients with active inflammatory bowel disease is morbigenous

AIM: To investigate the role of cryofibrinogen (CF) in active inflammatory bowel disease (IBD). METHODS: CF was assayed in 284 subjects: 61 with active and 63 with inactive ulcerative colitis (DC), 45 who had proctocolectomy, 35 with active and 20 with inactive Crohn's disease (CD), 40 with other diseases and 20 healthy controls. Trypsin inhibitor (TI) and TI antibody (TI-Ab) were measured in plasma and CF complex by ELISA. RESULTS: CF in active UC was strikingly high compared with all other groups (X2<0.001). Similarly, CF was significantly higher in active CD than in inactive CD or in controls (X2<0.01). In UC, high CF and TI-Ab were associated with the need for operations. Further, high CF, CF/fibrinogen ratio, low TI and high TI-Ab in plasma were associated with disease activity or refractoriness to medication. Elevated CF was not associated with acute reactants like C-reactive protein and white blood cell counts except for erythrocyte sedimentation rate, suggesting that elevated CF was not a consequence of acute inflammation. CONCLUSION: Elevated CF in active IBD appears to be morbigenous. CF promotes IBD via two main mechanisms, quenching of TI (an anti-inflammatory substance) and impairing microvascular perfusion by forming protein aggregates. CF may also serve as a biomarker of chronic IBD. Additional studies are warranted to fully evaluate the role of CF in IBD and the outcome should contribute to a better understanding of the pathogenesis of IBD.     

High plasma osteopontin levels in patients with inflammatory bowel disease

BACKGROUND: Osteopontin (OPN) plays a key role in the progression of T(H)1-immune-mediated disease in models of multiple sclerosis and rheumatoid arthritis. AIM: To determine whether plasma OPN levels in patients with inflammatory bowel disease are associated with disease activity. METHODS: Plasma samples were obtained from patients with ulcerative colitis (UC, n=30), Crohn's disease (CD, n=30), and healthy volunteers (controls, n=30) and enzyme immunoassay was performed. RESULTS: Plasma OPN concentrations were significantly higher in patients with Crohn's disease than in controls (951.9+/-538.5 ng/mL and 659.0+/-163.7 ng/mL, respectively). OPN concentrations in patients with UC were also higher than in the controls (1149.6+/-791.0 and 659.0+/-163.7, respectively). There was a significant difference in plasma OPN level between active UC and inactive UC (2102.0+/-552.8 and 649.4+/-313.0, respectively). Moreover, a significant correlation was observed between plasma OPN concentration and disease activity, as determined by the clinical activity index in patients with UC. CONCLUSIONS: Our results indicate that the plasma concentrations of OPN are elevated in patients with UC and that OPN expression is correlated with clinical activity. These results provide insight into UC pathogenesis and suggest that OPN may be a useful tool for assessing disease activity.     

Elevated pancreatic enzymes in inflammatory bowel disease are associated with extensive disease

OBJECTIVE: Our aim was to perform a cross-sectional study to estimate the prevalence of elevated pancreatic enzymes in patients with inflammatory bowel disease and to correlate the enzyme activities with clinical, endoscopic, and histological findings. METHODS: Two hundred thirty-seven patients diagnosed with inflammatory bowel disease (IBD), including a subgroup with known hepatobiliary disease, were studied crosssectionally. Serum and urinary pancreatic enzymes were prospectively sampled and compared to endoscopic and histological findings obtained previously. RESULTS: Hyperamylasemia was found in 11% and hyperlipasemia in 7% of the total study group. The corresponding prevalences in patients with Crohn's disease were 17% and 9%, those in ulcerative colitis 9% and 7%, and those in indeterminate colitis 10% and 5%, respectively. High levels of serum amylase and pancreatic isoamylase were associated with extensive colonic disease (p < 0.005) and high histological activity (p < 0.05). Amylase, but not lipase, was significantly elevated in patients with primary sclerosing cholangitis. Smokers showed higher urinary amylase levels than non- and ex-smokers. The use of medication had no influence on the enzyme levels. CONCLUSIONS: Pancreatic enzymes are elevated in a significant proportion of patients with IBD, and the enzyme increase is associated with a more extensive and active disease, and in some cases with primary sclerosing cholangitis.     

Elevated serum PIIINP and laminin in inflammatory bowel disease indicate hepatobiliary and pancreatic dysfunction

BACKGROUND/AIMS: Levels of S-PIIINP (serum aminoterminal propeptide of type III procollagen) have been shown to be increased in patients with primary sclerosing cholangitis and inflammatory bowel disease. The aim of the study was to investigate the serum concentrations of PIIINP and laminin in inflammatory bowel disease patients, their relationship with inflammatory bowel disease-associated hepatobiliary and pancreatic dysfunction, and to correlate them with clinical, endoscopic, and histologic variables. METHODOLOGY: S-PIIINP and S-laminin were measured in 222 consecutive inflammatory bowel disease patients, who were screened for abnormal liver and pancreatic enzymes and for pancreatic exocrine hypofunction with the p-aminobenzoic acid test (215 patients). The patients with abnormal screening results were further scheduled for endoscopic retrograde cholangiopancreatography, liver biopsy, secretin test and ultrasound. RESULTS: S-PIIINP and S-laminin were abnormally high in 19% and 40% of all inflammatory bowel disease patients, respectively. The elevated levels of the fibrosis markers were associated with laboratory signs of either hepatobiliary or pancreatic disease. Hepatobiliary disease was found in 37 (17%) of inflammatory bowel disease patients, 15 of whom had primary sclerosing cholangitis. The median levels of S-PIIINP and S-laminin were significantly higher in patients with hepatobiliary disease than in those without (P < 0.0001 and P < 0.001, respectively), being most strikingly elevated in primary sclerosing cholangitis. Abnormal pancreatic screening tests were found in 67 (30%) patients. High levels of S-PIIINP and S-laminin were also significantly associated with low values in p-aminobenzoic acid (P < 0.001 and P < 0.005) and secretin (P < 0.01 and P < 0.05) tests, but not with inflammatory bowel disease category, endoscopic or histological disease extent, frequency of bowel resection or actual clinical activity. CONCLUSIONS: In inflammatory bowel disease, increased S-PIIINP and S-laminin are associated with hepatobiliary and pancreatic disorders.     

Higher vedolizumab serum levels do not increase the risk of adverse events in patients with inflammatory bowel disease

Abstract

Background: Although its mechanism of action may confer a safety benefit, vedolizumab has still been associated with adverse events (AE). We investigated whether inflammatory bowel disease (IBD) patients with higher trough vedolizumab serum levels experienced an increased risk of AEs.

Methods: This was a retrospective study of 76 IBD patients with at least one measurement of serum vedolizumab available. Vedolizumab levels ranged from <3.5?mcg/mL to 87.2?mcg/mL (median = 15.8?mcg/mL). The primary outcome was the rate of overall AEs. Secondary outcomes included the rates of infections, dermatologic reactions, infusion reactions, and other AEs. Multivariate logistic regression analysis was performed to evaluate the relationship between serum vedolizumab levels and AEs.

Results: 19 patients out of 76 reported AEs. In patients with higher vedolizumab levels, there were 10 AEs reported out of 38 patients, which was not significantly different from the 9 AEs reported in 38 patients with lower vedolizumab levels (26.3% vs. 23.7%, p?=?.79). After adjustment for potential covariates, IBD patients with higher vedolizumab levels did not have higher odds of an AE than patients with lower levels (OR 0.92, 95% CI 0.30–2.81). Longer duration of therapy had higher odds of AEs, (OR of 1.04 at 95% CI 1.00–1.09, p?=?.0494 per additional month). None of the other variables were associated with a greater risk of AEs.

Conclusions: There does not appear to be an increased risk of adverse events in IBD patients with higher vedolizumab levels, but duration of therapy may increase the risk of AEs.     

Vaccinations in patients with inflammatory bowel disease

Treatment of inflammatory bowel disease (IBD) frequently requires administration of immunosuppressive therapies, which increases susceptibility to a number of infectious pathogens. However, many infections can be prevented by correct and appropriate utilization of vaccinations. While several guidelines have been published on vaccination schedules in patients with IBD, vaccination rates remain suboptimal and even lower than those in the general population. This is due to many factors including poor awareness of the importance of vaccines by gastroenterologists and general practitioners as well as potential prejudices of patients regarding the safety and benefits of vaccines. With the aim of increasing awareness about the key role of immunization in the management of patients with IBD, the present review examines the existing literature relating to the main vaccinations and their application in these patients. We also summarize current evidence in order to provide clinicians with an easy source of reference for the principal recommendations for prevention of infectious diseases in patients with IBD. In addition, the recommendations about traveling for IBD patients are briefly explored. Lastly, since it is important for gastroenterologists to be aware of recommendations on vaccination, we recommend implementing educational programs to ensure compliance with current guidelines.     

Communicating with patients with inflammatory bowel disease

Ulcerative colitis and Crohn's disease, the two main forms of inflammatory bowel disease (IBD), are chronic illnesses that affect hundreds of thousands of Americans. Patients with IBD suffer chronically from diarrhea, abdominal pain, gastrointestinal bleeding, malabsorption, and weight loss requiring continuous medical and surgical attention. Despite recent advances in therapy, IBD follows a course of exacerbations and remissions with approximately 25-50% of patients relapsing annually. Hence, these diseases are readily encountered in primary care and gastroenterology clinics. Though medical and surgical treatment options have improved significantly, little has been written about the psychosocial aspects of IBD. Currently, there is a paucity of data concerning effective communication methods enabling physicians to develop stronger rapport with patients suffering from IBD, the care of whom requires a multidisciplinary approach involving primary care physicians, gastroenterologists, and colorectal surgeons. Because IBD has a high morbidity, it is worthwhile to further investigate those social factors that will improve patients' quality of life. In this paper, we summarize some of the common problems that emerge when taking care of patients with IBD and provide initial guidelines based on the world literature regarding the management and education of patients with IBD. Both primary care physicians and specialists (gastroenterologists, colorectal surgeons) need to be aware of the questions and concerns of IBD patients and to be capable of dispensing the information in a clear and concise manner. Using the case scenario format, we review the most common aspects of communication for health care professionals taking care of IBD patients and suggest ways to establish and maintain long-term doctor-patient relationships. The two most significant interventions that dramatically improve quality of life and patient-physician relationships are proper patient education and appropriate treatment of concurrent depression and anxiety. We hope that our review will form a framework by which different members of the medical team learn their roles in the complex management decisions affecting IBD patients.     

Role of serum procalcitonin in evaluating disease activity of 107 patients with inflammatory bowel disease

正Objective To preliminarily investigate the clinical value of serum procalciton as a non-invasive marker in disease activity assessment in inflammatory bowel disease(IBD).Methods From January 2014 to June 2016,clinical data of 107 IBD patients were collected,including biological inflammatory parameters of peripheral blood such as serum procalcitonin levels,C-reactive protein(CRP)levels,erythrocyte sedimentation rate(ESR)and platelet count,clinical disease activity scores and