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.     

Serum YKL-40, a potential new marker of disease activity in patients with inflammatory bowel disease

BACKGROUND: YKL-40 is secreted by macrophages and neutrophils and is a growth factor for vascular endothelial cells and fibroblasts. Elevated serum concentrations of YKL-40 are found in patients with diseases characterized by inflammation or ongoing fibrosis. The aim of this study was to seek association between serum YKL-40 in patients with ulcerative colitis (UC) and Crohn disease (CD) and clinical disease activity. METHODS: One-hundred-and-sixty-four patients with UC and 173 patients with CD were studied. The Simple Clinical Colitis Activity Index (SCCAI) and the Harvey-Bradshaw (H-B) score were used to assess disease activity. Serum YKL-40 (determined by ELISA) was related to C-reactive protein (CRP) and disease activity. RESULTS: In patients with UC, the median serum YKL-40 rose with increasing disease activity, and patients with severe active disease had higher serum YKL-40 (median 59 microg/L (95% CI: 26-258 microg/L), P < 0.001) than patients with inactive UC (33 microg/L (19-163)) and age-matched controls (43 microg/L (20-124)). Patients with severe active CD had higher serum YKL-40 (59 microg/L (21-654), P < 0.001) than age-matched controls, but not higher than inactive CD patients (43 microg/L (17-306)). Serum YKL-40 was elevated in 41% of the patients with severe UC, in 10% with inactive UC, in 46% with severe CD and in 30% with inactive CD. Serum YKL-40 correlated with SCCAI in UC patients but not with H-B score in CD patients. In both patient groups, low correlations were found between serum YKL-40 and CRP, albumin and leucocytes. CONCLUSIONS: Serum YKL-40 is elevated in patients with active IBD and may be complementary to inflammatory markers and clinical characteristics in the assessment of disease activity.     

Elevated serum eotaxin levels in patients with inflammatory bowel disease

OBJECTIVE: Eotaxin is a recently characterized chemokine with potent and selective chemotactic activity for eosinophils. Previous studies indicating that eosinophils accumulate and become activated in inflammatory bowel disease (IBD) led us to hypothesize that eotaxin is potentially involved in the pathophysiology of IBD and, therefore, that eotaxin would be increased in the serum of patients with IBD. The objective of this study was to test those assumptions. METHODS: We investigated 72 patients with IBD, 35 with ulcerative colitis, and 37 with Crohn's disease. A total of 27 patients had active and 45 inactive disease; 26 were receiving corticosteroids. Eotaxin serum levels were determined by solid phase sandwich ELISA. Lymphocytes, monocytes, and granulocyte subpopulations were determined in fresh blood samples with an automated autoanalyzer. RESULTS: Serum eotaxin levels were significantly higher in patients with Crohn's disease and in those with ulcerative colitis than in the control subjects (p < 0.0001). Patients with inactive Crohn's disease had significantly higher levels of eotaxin than patients with inactive ulcerative colitis (p < 0.05). We did not find significant differences for activity or inactivity of disease, nor for treatment with prednisone. A negative correlation (p < 0.05) was found between eotaxin serum level and eosinophil counts in peripheral blood in patients with Crohn's disease. CONCLUSIONS: There is an increased expression of eotaxin in IBD patients, suggesting that eotaxin may be involved in the pathogenesis of IBD. This increase is more accentuated in Crohn's disease and negatively correlates with the eosinophil number in peripheral blood. Our data support the increasing evidence that eosinophil are functionally involved in the pathophysiology 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 YKL-40 and C-reactive protein levels are associated with angiographic lesion progression in patients with coronary artery disease

Objective

YKL-40 is a pro-inflammatory protein highly expressed in atherosclerotic plaques, and is related to prognosis of patients with coronary artery disease (CAD). This study aimed to assess the possible association between YKL-40 and coronary lesion progression in CAD patients.

Methods

A total of 313 patients with CAD, who underwent percutaneous coronary intervention (PCI) and follow-up angiography (mean 13.2 ± 3.2 months) were recruited. Serum YKL-40 and high-sensitivity C-reactive protein (hsCRP) levels were measured using ELISA kits.

Results

Baseline serum YKL-40 and hsCRP levels were higher in those with lesion progression (all p < 0.001 vs. patients without lesion progression), and correlated significantly with change of lumen diameter stenosis and cumulative coronary obstruction score (all p < 0.01). Multivariable logistic regression analysis revealed that after adjusting for conventional risk factors, number of total coronary artery lesions, YKL-40 and hsCRP levels were independent determinants of lesion progression. An area under the curve of YKL-40 and hsCRP was 0.744 (CI 95% 0.685–0.804, p < 0.001) and 0.716 (CI 95% 0.657–0.776, p < 0.001), respectively. The optimal values of cut-off point were 74.98 ng/ml (sensitivity 70%, specificity 71%) for YKL-40 and 3.21 mg/l (sensitivity 66%, specificity 68%) for hsCRP to predict lesion progression.

Conclusion

Increased serum YKL-40 and hsCRP levels are independently associated with lesion progression in patients with CAD.     

Serum YKL-40 levels in patients with coronary artery disease

Atherosclerosis is considered to be an inflammatory disease in which the initial process is the augmented infiltration of monocytes into the vessel wall and their subsequent differentiation from macrophages into lipid-laden foam cells. Human cartilage glycoprotein-39 (YKL-40) is a new inflammatory marker found to be secreted by lipid-laden macrophages inside human atherosclerotic vessel wall. The aim of this study was to investigate the association of serum YKL-40 levels with the presence and extent of coronary artery disease (CAD) assessed by coronary angiography. We also studied the relation of high-sensitivity C-reactive protein with the presence and angiographic severity of CAD. A total of 200 participants undergoing to coronary angiography was divided into four subgroups: control patients without CAD (n=53), and those with one-vessel disease (n=52), two-vessel disease (n=47), or three-vessel disease (n=48). Serum YKL-40 levels were measured by enzyme-linked immunosorbent assay. Both serum YKL-40 levels and high-sensitivity C-reactive protein concentrations in patients with CAD were significantly higher than in control participants (P<0.001). We also found a significant association between the levels of YKL-40 and the extent of CAD defined by the number of stenosed vessels (P<0.001). The relationship between the serum YKL-40 level and atherosclerosis may represent a new opportunity for the possible utility of serum YKL-40 as an inflammatory marker for coronary artery disease. Moreover, our findings revealed that plasma YKL-40 measurement might also be regarded as a quantitative indicator of disease extent besides being a marker of disease presence.     

The relationship between serum levels of YKL-40 and disease progression in patients with early rheumatoid arthritis

YKL-40 concentrations in serum were determined by an ELISA at 3 occasions during 19 months for 57 early RA patients. The results were related to biochemical and radiographic measures at each time point. YKL-40 correlated significantly to ESR and CRP throughout the study. Correlations between YKL-40 and radiographic findings scored by the Larsen method were fairly weak both for absolute values at each time point (Rs 0.212-0.319) and for progression over time (Rs 0.152-0.301). Baseline YKL-40 could predict radiographic progression with a specificity and sensitivity of only slightly over 50%. ESR and CRP correlated stronger than YKL-40 to joint damage progression and in a multiple regression model ESR was the only significant variable explaining the variance of this radiographic measure. We conclude that serial measurements of serum YKL-40 did not provide information that could not be obtained by conventional biochemical measures of disease activity.     

川崎病合并冠状动脉病变患者血清Ang-1、YKL-40水平与凝血功能、炎症反应的相关性

目的]探究川崎病(KD)合并冠状动脉病变(CAL)患者血清血管生成素1(Ang-1)、人软骨糖蛋白39(YKL-40)水平与凝血功能、炎症反应的相关性。 [方法]选取2018年1月─2022年12月收治的90例KD患者作为研究对象,选取同期在本院检查健康的90名儿童为对照组,根据是否合并CAL,分为未合并CAL组(69例)和合并CAL组(21例),比较各组血清Ang-1、YKL-40、凝血功能和炎症因子水平。采用Pearson分析法分析KD合并CAL患者血清Ang-1、YKL-40水平与凝血功能、炎症反应指标的关系,采用多因素Logistic回归分析影响KD患者发生CAL的因素。 [结果]对照组、未合并CAL组、合并CAL组血清Ang-1、YKL-40水平比较差异有统计学意义(均P＜0.05);随着病情严重程度的增加,对照组、未合并CAL组、合并CAL组血清Ang-1水平逐渐降低,YKL-40水平逐渐升高(均P＜0.05)。血清Ang-1与纤维蛋白原(FIB)、C反应蛋白(CRP)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、白细胞计数(WBC)呈负相关(均P＜0.05),YKL-40与FIB、CRP、TNF-α、IL-6、WBC呈正相关(均P＜0.05)。多因素Logistic回归分析显示,YKL-40是影响KD患者并发CAL的危险因素,Ang-1为其保护因素(P＜0.05)。 [结论]KD合并CAL患者血清Ang-1水平降低、YKL-40水平升高,与凝血功能、炎症反应有一定的相关性。     

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.     

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.     

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.     

Increased aggregation response of platelets in patients with inflammatory bowel disease

Background Platelets play an important role in hemostatic and inflammatory responses. To evaluate any potential enhancement of platelet activity in patients with inflammatory bowel disease (IBD), we measured the platelet aggregation responses to various stimuli. Methods Twenty-two healthy controls, 24 patients with ulcerative colitis (UC) and 25 patients with Crohn's Disease (CD) were studied. The aggregation responses induced by three agonists (epinephrine, collagen, and ADP) were measured by an 8-channel aggregometer. The platelet-derived microparticles (PDMP) levels were measured by an enzyme-linked immunosorbent assay. Results Twenty-one out of the 22 healthy controls did not respond to epinephrine (0.1 μg/ml), collagen (0.2 μg/ml), or ADP (1.0 μM). Eight out of the 12 active UC patients were sensitive to all agonists, and 4 patients showed increased sensitivity to epinephrine/collagen or epinephrine/ADP. Three out of the 12 inactive UC patients were normal, but 9 of these patients showed increased sensitivity, mainly to epinephrine. Ten out of the 12 active CD patients were sensitive to all agonists, and 2 active CD patients were sensitive to epinephrine/collagen or epinephrine/ADP. Eight out of the 13 inactive CD patients were sensitive to two or all agonists. Even after remission, almost all of the UC and CD patients showed some increased sensitivity to the agonists. The platelet number and the plasma PDMP levels were significantly higher in the active IBD patients than in the control group. Conclusions Platelet aggregation responses are enhanced in IBD, even in inactive-phase patients. This increased sensitivity of the platelets may play an important role in the pathophysiology of IBD.     

Increased risk for demyelinating diseases in patients with inflammatory bowel disease

BACKGROUND & AIMS: Reports of multiple sclerosis (MS), demyelination, and optic neuritis (ON) associated with anti-tumor necrosis factor alpha therapy resulted in warnings on prescribing instructions for infliximab, etanercept, and adalimumab. However, the underlying relationship between IBD and these neurologic conditions has not been established. METHODS: We performed a retrospective cohort study and a retrospective cross-sectional study using 1988 to 1997 data from the General Practice Research Database. A total of 7988 Crohn's disease and 12,185 ulcerative colitis patients were matched for age, sex, and primary care practice to 80,666 randomly selected controls. In the cohort study, incident cases of MS, demyelination, and/or ON (MS/D/ON) had to occur at least 1 year after registration with the physician and after the diagnosis of IBD. In the cross-sectional study, the diagnosis of MS/D/ON could either precede or follow the IBD diagnosis. RESULTS: In the cohort study, the incidence of MS/D/ON was higher in patients with Crohn's disease and ulcerative colitis compared with their matched controls, reaching statistical significance for ulcerative colitis (ulcerative colitis incidence rate ratio [IRR], 2.63; 95% confidence interval, 1.29-5.15; Crohn's disease IRR, 2.12; 95% confidence interval, .94-4.50). In the cross-sectional study, MS/D/ON was more prevalent in patients with Crohn's disease and ulcerative colitis compared with their matched controls (Crohn's disease odds ratio, 1.54; 95% confidence interval, 1.03-2.32; ulcerative colitis odds ratio, 1.75; 95% confidence interval, 1.28-2.39). CONCLUSIONS: Demyelinating diseases occur more commonly among patients with IBD than among non-IBD patients. Future studies should clarify whether treatment with tumor necrosis factor alpha blockers results in further increased incidence of MS/D/ON among IBD patients.     

High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement

OBJECTIVES: YKL-40, a growth factor of connective tissue cells, is elevated in sera from patients with diseases characterized by inflammation, tissue remodelling, or fibrosis. The aim of the study was to determine serum YKL-40 levels in patients with systemic sclerosis (SSc) and to explore any possible clinical and prognostic associations. METHODS: YKL-40 was measured in sera from 88 patients with SSc (26 with diffuse and 62 with limited skin involvement) and in sera from 88 matched healthy controls. Immunohistochemical staining for YKL-40 antigen was performed in a biopsy from a patient with pulmonary SSc. RESULTS: Serum YKL-40 levels of the SSc patients were significantly higher than those of the controls (p<0.00001). Patients with pulmonary fibrosis by chest X-ray, obstructive ventilatory pattern, reduced diffusing capacity (DLco), and digital joint deformity due to skin retraction had significantly higher serum YKL-40 compared with patients without these findings. Patients with elevated serum YKL-40 had shorter survival times than patients with normal serum YKL-40 (p = 0.0005), although this was not independent of age and pulmonary function. YKL-40 protein expression was found in inflammatory cells in fibrosing pulmonary tissue from a patient with SSc. CONCLUSIONS: Serum YKL-40 is elevated in patients with SSc with pulmonary involvement.     

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.     

Increased serum soluble CD40 levels in patients with systemic sclerosis

OBJECTIVE: To determine serum levels of soluble CD40 (sCD40) and clinical association in patients with systemic sclerosis (SSc). METHODS: Serum sCD40 levels were examined by ELISA in 49 patients with SSc, 15 patients with systemic lupus erythematosus, and 26 healthy individuals. sCD40 levels in plasma samples, which were obtained at the same time, were also determined. SSc patients were grouped into 22 patients with limited cutaneous SSc (lcSSc) and 27 patients with diffuse cutaneous SSc (dcSSc). RESULTS: There was no significant difference between sCD40 levels of sera and those of plasma. Serum sCD40 levels were significantly elevated in patients with SSc compared to patients with systemic lupus erythematosus and controls (p < 0.001). Serum sCD40 levels were higher in patients with lcSSc than in those with dcSSc (p <0.001). There was no correlation between sCD40 and sCD40 ligand levels in patients with SSc. CONCLUSION: Elevated serum sCD40 levels were associated with lcSSc. These results suggest that the blockade of CD40/CD40 ligand interaction could be a potential therapeutic strategy in SSc.     

Increased catabolism and decreased unsaturation of ganglioside in patients with inflammatory bowel disease

AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease(n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps(n = 6) and colorectal cancer(n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1 a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine(PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A(HEXA) and sialidase-3(NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher(P 0.05) in intestine from patients with inflammatory bowel disease(IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue(P 0.05). Control intestine exhibited 3-fold higher(P 0.01) relative GD1 a ganglioside content than IBD intestine. GD3 and GD1 a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine(P 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold(P 0.05) and NEU3 was increased 8.3-fold(P 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1 a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1 a and PC.CONCLUSION: This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides.     

Increased expression of VEGF and CD146 in patients with inflammatory bowel disease

BACKGROUND: Angiogenesis has been suggested as an integral part of inflammatory bowel disease pathology. Vascular endothelial growth factor has long been considered to play a central, specific role in angiogenesis. Endothelial junction adhesion molecules, such as CD146, have recently been suggested to play a potent role in angiogenesis. CD34 is expressed on vascular endothelium, and it has been reported to be upregulated on endothelium in IBD. We investigated the expression of tissue vascular endothelial growth factor, CD34 and CD146 in the inflamed mucosa of patients with active inflammatory bowel disease compared with no inflamed mucosa of healthy controls. METHODS: Forty-two IBD patients [23 ulcerative colitis, 19 Crohn's disease] and ten healthy controls were included in the study. In colonoscopically obtained biopsies, CD34, CD146 and vascular endothelial growth factor expression were evaluated by immunohistochemistry. RESULTS: Vascular endothelial growth factor was detected in the mucosa of all groups, and its expression was significantly higher in both Crohn's disease and ulcerative colitis compared with controls (p<0.05). Immunohistochemical staining for CD146 in the inflamed mucosa was significantly higher in both Crohn's disease and ulcerative colitis compared with controls (p=0.002). A trend of higher CD34 expression in Crohn's disease and ulcerative colitis compared with controls was also found, but the difference among the three groups was not statistically significant (p=0.09). CONCLUSIONS: Inflamed mucosa of patients with active Crohn's disease and ulcerative colitis showed a markedly enhanced expression of VEGF and CD146, than normal mucosa of controls, indicating a possible role of angiogenesis in the pathogenesis of inflammatory bowel disease.     

Increased expression of markers of early atherosclerosis in patients with inflammatory bowel disease

Background & AimsRecent studies documented an increased cardiovascular risk in patients with inflammatory bowel disease (IBD). Our study aimed at investigating the prevalence of intima-media thickness (IMT) of the carotid arteries and the arterial stiffness indices as markers of early atherosclerosis in young IBD patients.MethodsWe recruited 68 consecutive IBD patients, and 38 matched healthy controls less than 45 years old (median age 31.6 ± 8.1 years). Clinical and demographic features, cardiovascular risk factors, history of cardiovascular events, concomitant therapies were registered on a dedicate database. Carotid IMT was evaluated by using high resolution B-mode ultrasonography. Arterial stiffness was assessed by measurement of carotid-femoral Pulse Wave Velocity (PWV) and Augmentation Index (AIx).ResultsTotal cholesterol (P < 0.013) and LDL-cholesterol (P < 0.019) levels were significantly lower in IBD patients compared to controls. Carotid IMT was higher in IBD than in controls (P < 0.047), but there was no statistically significant difference among Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. Moreover, PWV and AIx were significantly higher in patients as compared to controls (P < 0.006 and P < 0.004 respectively). No medication seemed to affect vascular measurements, though stiffness parameters were significantly higher in patients treated with 5-ASA (11.9 (9.7) vs 18.2 (10.2), P < 0.021), suggesting a lack of efficacy of 5-ASA in protecting IBD patients from early atherogenesis.ConclusionsYoung IBD patients show an increase in subclinical markers of atherosclerosis. Future studies need to address whether these markers result in an increased risk of cardiovascular events in these patient.