Leucine-rich a-2 glycoprotein as a potential biomarker of idiopathic multicentric Castleman disease with pulmonary involvement: a single-center case-control study from Japan

BackgroundThere are no known biomarkers for monitoring disease activity in idiopathic multicentric Castleman disease (MCD) with pulmonary involvement. We investigated the utility of serum leucine-rich α2-glycoprotein levels, which reflects interleukin 6 independent inflammatory change, for monitoring disease activity in patients with idiopathic MCD with pulmonary involvement.MethodsWe retrospectively examined cases of idiopathic MCD diagnosed at Osaka University Hospital. The serum levels of leucine-rich α2-glycoprotein were compared between patients with idiopathic MCD and healthy controls. The difference in leucine-rich α2-glycoprotein levels before and after treatment (∆leucine-rich α2-glycoprotein) was evaluated with respect to the relationship with pulmonary function. In addition, the relationship between cytokine and chemokine profiles and the leucine-rich α2-glycoprotein concentration was investigated. The results were analyzed using pathway analysis.ResultsThe leucine-rich α2-glycoprotein concentrations were significantly higher in treatment-naïve patients (n=5) than in healthy controls (n=3) (P=0.035). Further, the ∆leucine-rich α2-glycoprotein concentration was significantly correlated with ∆ percent diffusing capacity of the lung for carbon monoxide (r=−0.88, P=0.049) and tended to correlate with ∆ percent vital capacity (r=−0.68, P=0.21) although the difference was not significant for the latter association. The concentrations of chemokines and cytokines, such as CXCL9, CXCL11, CXCL1, and a proliferation-inducing ligand, were higher in the patient group than in the healthy control group. Enrichment analysis indicated that leucine-rich α2-glycoprotein could be elevated via the upregulation of chemokines in patients with idiopathic MCD using these parameters.ConclusionsLeucine-rich a2-glycoprotein may be useful for monitoring disease activity in patients with idiopathic MCD with pulmonary involvement.     

Urinary leukotriene E4 excretion: a biomarker of inflammatory bowel disease activity

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders collectively referred to as inflammatory bowel diseases (IBD). Cysteinyl leukotrienes are proinflammatory 5-lipoxygenase-derived products that play a major role in the immune and inflammatory response. Consequently, they may be involved in the pathogenesis of IBD. The aim of this study was therefore to evaluate 1) the urinary excretion of leukotriene E(4) (LTE(4)) in IBD patients and healthy volunteers, and 2) the association between LTE(4) production and the activity (relapse/remission) of the disease. METHODS: IBD patients and healthy volunteers were prospectively recruited. CD and UC activity was determined on inclusion with the Crohn's Disease Activity Index and Clinical Activity Index, respectively. Urine was collected and the urinary excretion of LTE(4) was measured by liquid chromatography tandem mass spectrometry. RESULTS: 32 CD patients, 28 UC patients, and 30 controls were enrolled in the study. LTE(4) urinary excretion was significantly increased (P < 0.01) in CD [52.0 pg/mg creatinine (10th-90th percentiles: 26.2-148.0)] and UC [64.1 pg/mg creatinine (10th-90th percentiles: 26.7-178.0)] patients compared to controls [32.3 pg/mg creatinine (10th-90th percentiles: 21.8-58.8)]. LTE(4) levels were higher (P < 0.001) in patients with active disease than in patients in remission, for whom the levels of LTE(4) were similar to the levels of controls. CONCLUSIONS: Cysteinyl leukotriene pathway activation could contribute to the inflammation associated with IBD. The quantification of urinary LTE(4) could be an interesting noninvasive biomarker for the assessment of IBD activity.     

Chromogranin A as a biomarker of disease activity and biologic therapy in inflammatory bowel disease: a prospective observational study

Abstract

Objective. To access the correlation of Chromogranin A (CgA) with inflammatory bowel disease (IBD) activity and responsiveness to medical therapy. Material and methods. A prospective observational study was conducted in 56 patients with moderate ulcerative colitis (UC) or Crohn’s disease (CD) (UC, n = 29, CD, n = 27), 17 patients with irritable bowel syndrome and predominant diarrhea (IBS-D) and 40 healthy volunteers. IBD patients were treated by biologics (infliximab or adalimumab) or conventional agents (aminosalicylates, thiopurines or methotrexate and steroids) and were classified according to their treatment in two groups. Serum CgA was measured at baseline and 4-week posttreatment period. Results. Serum CgA was significantly higher in IBD patients than in those with IBS-D or healthy volunteers (p < 0.01). Furthermore, serum CgA was markedly increased in CD patients than in UC patients (p < 0.01). CgA value was significantly reduced in ‘biologic’ group (24 IBD patients, UC, n = 15, CD, n = 9) at 4-week posttreatment period (p < 0.01), while 18/24 (72%) patients were already in remission during that time. In contrast, CgA value was significantly increased in the ‘conventional’ treatment group (32 IBD patients, UC, n = 14, CD, n = 18) between the two visits (p < 0.01), although 22/32 (69%) patients were in remission during the 4-week posttreatment period. Conclusion. CgA appears to be a reliable marker of disease activity in IBD patients and especially in those who received biologic therapy. IBS-D patients presented normal CgA values.     

Serum beta 2-microglobulin as a biomarker in inflammatory bowel disease

AIM: To investigate the diagnostic utility of beta 2 microglobulin (B2-M) levels and analyze this correlation with the activity of inflammatory bowel disease (IBD).METHODS: Overall, 78 IBD patients and 30 healthy controls were enrolled in the study. We examined B2-M serum levels in 43 ulcerative colitis (UC) patients, 35 with Crohn’s disease (CD) and 30 control subjects, using an enzymatic method. Patients were divided into two groups according to two disease types: active and in remission. Subjects were also divided into two subgroups according to extent of the disease: left-side and pancolitis for UC and ileitis and ileocolitis for CD. All groups were compared for mean serum B2-M levels and also examined to see whether there was a correlation between serum B2-M levels and other inflammatory markers.RESULTS: The mean serum B2-M levels in the control group, UC and CD were 1.71, 2.41 and 2.24 respectively. B2-M values ≥ 1.96 mg/L had a 62% sensitivity, 76% specificity, a 79% positive predictive value, and a 58% negative predictive value for UC patients. B2-M values ≥ 1.70 mg/L had 80% sensitivity, 53% specificity, 66% positive predictive value, and 69% negative predictive value for CD patients. Mean B2-M values were significantly higher in ulcerative colitis and Crohn’s disease patients than in healthy controls (UC 2.41 ± 0.87 vs 1.71 ± 0.44, P = 0.002; CD 2.24 ± 1.01 vs 1.71 ± 0.44, P = 0.033). Also, mean B2-M values were significantly higher in active disease when compared to patients in remission (UC 2.66 ± 0.92 vs 1.88 ± 0.41, P = 0.004; CD 2.50 ± 1.15 vs 1.73 ± 0.31, P = 0.033). The difference between groups (UC and CD) in terms of serum B2-M levels was statistically insignificant (2.41 ± 0.87 vs 2.24 ± 1.01, P > 0.05 respectively).CONCLUSION: Serum B2-M levels may be used as an activity parameter in IBD.     

Novel approaches to treating inflammatory bowel disease: targeting alpha-4 integrin

Crohn's disease involves persistent recruitment of leukocytes into gut tissue, coupled with dysregulated activation of specific immune cell function. Adhesion molecules expressed by circulating leukocytes, such as alpha 4 integrin, mediate their attachment to vascular endothelial cells lining blood vessels within the intestine and facilitate their migration into the tissue. Through interactions with extracellular matrix molecules, adhesion molecules then support immune cell activation and survival within the intestinal wall. Agents that interfere with these adhesive interactions hold great potential for suppressing the cycle of leukocyte infiltration and activation, and thereby, for ameliorating chronic inflammation. This article will discuss clinical data for a humanized monoclonal antibody against alpha 4 integrin, natalizumab, which is the first alpha 4 integrin antagonist in a new class of biotechnology agents referred to as selective adhesion molecule inhibitors.     

Intestinal ultrasound as a non-invasive tool to monitor inflammatory bowel disease activity and guide clinical decision making

Intestinal ultrasound(IUS) is a non-invasive, real-time, cross-sectional imaging tool that can be used at the point-of-care to assess disease activity in patients with Crohn’s disease or ulcerative colitis. IUS promotes quick and impactful treatment decisions that can modify disease progression and enhance patient compliance. This review will summarize the technical aspects of IUS, the evidence to support the use of IUS in disease activity monitoring, the comparison of IUS to current standard of...     

Mortality in inflammatory bowel disease: a population-based cohort study

BACKGROUND & AIMS: There is no consensus regarding any increase in mortality with inflammatory bowel disease (IBD). In general, previous studies were not contemporary and were unable to correct for likely confounders. We have performed a large cohort study to examine contemporary IBD related mortality in the United Kingdom. METHODS: We selected subjects within the General Practice Research Database with a coded diagnosis of inflammatory bowel disease and up to 5 matched controls for each. We derived the date of recorded deaths and information on smoking and a variety of medical conditions. We calculated both the absolute risk of death and the relative risk as a hazard ratio corrected for available confounders by Cox regression. RESULTS: We included 16,550 IBD cases with 1047 deaths and 82,917 controls with 3758 deaths. The mortality rate was 17.1 per 1000 person-years overall for IBD cases and 12.3 for controls; this difference was greatest in the elderly. Conversion of these figures to hazard ratios by Cox regression gave hazard ratios of 1.54 (1.44-1.65) for all IBD, 1.44 (1.31-1.58) for ulcerative colitis (UC), and 1.73 (1.54-1.96) for Crohn's disease. The greatest hazard ratio for UC was among the 40-59-year age group (1.79 [1.42-2.27]) and for Crohn's disease among 20-39-year-olds (3.82 [2.17-6.75]). CONCLUSIONS: IBD is associated with an overall small increase in mortality rate greatest in relative terms in younger subjects but in absolute terms in the elderly.     

Pulmonary manifestations in inflammatory bowel disease: a prospective study

Background

Although pulmonary abnormalities have been recognized in patients with inflammatory bowel diseases (IBD), their prevalence and clinical significance are not known.

Aim

To study the prevalence and clinical significance of pulmonary abnormalities in patients with IBD.

Methods

Ninety-five non-consecutive patients with IBD (12 Crohn’s disease, 83 ulcerative colitis; mean age 41.9 [SD 13] years; 47 women) were prospectively studied from January 2007 to March 2010. Pulmonary function tests (PFT) and high-resolution CT (HRCT) chest were performed in them. PFT were compared to those in 270 healthy (control) subjects matched for age, sex and smoking status.

Results

Twenty-seven (28.5%) patients and 11 (4%) control subjects had abnormal PFT (p?Conclusion PFT and HRCT chest showed abnormality in about one-quarter of patients with IBD. A majority of patients with these abnormalities were asymptomatic.     

Lactosylceramide in inflammatory bowel disease: a biochemical study.

A simple technique for isolating lipids from small pieces of tissue was applied to mucosal biopsies and samples of resected intestine from patients with inflammatory bowel disease. Scanning densitometry of two dimensional chromatograms showed increased concentrations of the membrane associated glycosphingolipid lactosylceramide in Crohn's disease, on comparison with ulcerative colitis (p less than 0.01), or controls (p less than 0.01). This indicates either that normal glycosphingolipid metabolism is altered, or that a novel source of lactosylceramide is present in the inflamed mucosa of patients with Crohn's disease.     

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.     

Ischaemic colitis mimicking inflammatory bowel disease in a young adult receiving oral anticoagulation

Ischaemic colitis (IC) is the most frequent form of gastrointestinal ischaemia. Discrepancy between non-specific symptoms and objective findings is a hallmark of IC. Thus delay of diagnosis is common due to its often subtle and unpredictable presentation. In particular, the clinical symptoms and signs of IC can overlap with those of inflammatory bowel disease. We present a case of a young man with known factor-V-Leiden mutation in whom IC developed during effective therapy with oral anticoagulants, presenting with symptoms and endoscopic findings suggestive of inflammatory bowel disease.     

Ischaemic colitis mimicking inflammatory bowel disease in a young adult receiving oral anticoagulation

Ischaemic colitis (IC) is the most frequent form of gastrointestinal ischaemia. Discrepancy between non-specific symptoms and objective findings is a hallmark of IC. Thus delay of diagnosis is common due to its often subtle and unpredictable presentation. In particular, the clinical symptoms and signs of IC can overlap with those of inflammatory bowel disease. We present a case of a young man with known factor-V-Leiden mutation in whom IC developed during effective therapy with oral anticoagulants, presenting with symptoms and endoscopic findings suggestive of inflammatory bowel disease.     

Serum-soluble TRAIL: a potential biomarker for disease activity in myositis patients

Clinical Rheumatology - Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a member of the TNF super-family, which is involved in the regulation of immune response and...