MRP8/14 does not contribute to dissemination or inflammation in a murine model of Lyme borreliosis

Myeloid-related protein (MRP)8 and MRP14 form a complex (MRP8/14) that is released by activated neutrophils and monocytes during infection. MRP8/14 has been shown to have bacteriostatic activity in vitro against Borrelia burgdorferi, the spirochete that causes Lyme borreliosis. Furthermore, levels of MRP8/14 have been shown to be elevated in the joints of patients with Lyme arthritis. We hypothesized that MRP8/14 has a protective effect during B. burgdorferi infection. To determine the role of MRP8/14 in the immune response to B. burgdorferi, we studied the course of B. burgdorferi infection in wildtype (wt) and mrp14^?/? mice. In addition, we studied the response of leukocytes from mice lacking MRP8/14 to B. burgdorferi ex vivo. We demonstrated similar levels of B. burgdorferi dissemination, cytokine and immunoglobulin production in infected wt and mrp14^?/? mice after 21 days. Neutrophils and monocytes lacking MRP8/14 were undiminished in their ability to become activated or phagocytose B. burgdorferi. In conclusion, we did not find a central role of MRP8/14 in the immune response against B. burgdorferi. As the levels of MRP8/14 in the serum of infected mice were low, we speculate that MRP8/14 is not released in levels great enough to influence the course of B. burgdorferi infection.     

Assessment of ileal pouch inflammation by single-stool calprotectin assay

PURPOSE: Assessment of inflammation within the ileal pouch to establish a diagnosis of pouchitis requires both pouch endoscopy and biopsy because there can be a poor correlation between macroscopic and histologic assessments of inflammation. A simplified diagnostic test would be of clinical advantage. Calprotectin is a stable myelomonocytic protein, measurable in feces. It quantitatively relates to inflammation within the gastrointestinal tract. This study was designed to compare single and 24-hour stool measurements of calprotectin in patients with and without evidence of ileal pouch inflammation with endoscopic, histologic, and immunohistochemical indices. METHODS: Twenty-four-hour stool collections were made in ileal pouch patients, 9 with and 15 without (7 with ulcerative colitis and 8 with familial polyposis coli) evidence of pouch inflammation. First-morning stool concentration and total 24-hour calprotectin were quantified by use of a single step enzyme-linked immunosorbent assay. Biopsies from the reservoir were taken for conventional histology and scoring of intraepithelial neutrophil infiltrate. Cells positive for CD3, CD45RO, CD14, and CD15 within the lamina propria were quantified by use of immunohistochemistry. RESULTS: The mean first-morning stool calprotectin concentration correlated with the 24-hour level (r=0.91;P=<0.0001). The median single-stool calprotectin concentrations were 39 mg/l, 4 mg/l, and 8.5 mg/l (normal range, 0.2–10 mg/l) in patients with inflamed, noninflamed ulcerative colitis, and familial adenomatous polyposis, respectively. All nine patients with endoscopic and histologic evidence of pouch inflammation had raised stool calprotectin. Two of 15 patients without evidence of pouch inflammation had abnormal stool calprotectin. Single-stool calprotectin concentration correlated with the percentage of mature granulocytes (CD15;r=0.46;P=0.04) and activated macrophages (CD14;r=0.65;P=0.006), but not memory T cells (CD45RO;r=–0.05;P=0.4) within the lamina propria. CONCLUSION: Single first-morning stool calprotectin levels provide a quantitative measure of pouch inflammation, which may be helpful in the diagnosis and assessment of pouchitis.Supported by a grant from the Henry Smith Foundation.Presented at the Faulk symposium on the pelvic ileal reservoir in ulcerative colitis, Oxford, United Kingdom, April 17 to 19, 1997.     

Noninvasive Monitoring After Azathioprine Withdrawal in Patients With Inflammatory Bowel Disease in Deep Remission

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Serum calprotectin levels in elderly males and females without bacterial or viral infections

Objectives

Calprotectin is released from activated leukocytes and calprotectin can thus be used as a marker for leukocyte activation. Faeces calprotectin is not only used as a marker for inflammatory bowel disease but can also be used to detect leukocyte activation in other body fluids. The aim of the present study was to study serum calprotectin levels in non-infected elderly individuals to establish reference intervals for the marker.

Methods

Serum calprotectin was analyzed by immunoturbidimetry in 75 year old females and males without known infections. Individuals with CRP > 20 mg/L were excluded as this could indicate a subclinical infection. The calprotectin levels in the remaining 713 individuals were used to calculate reference values for this population. The Spearman rank correlations between calprotectin and 27 other laboratory biomarkers were also investigated.

Results

There was a strong positive Spearman rank correlation between calprotectin and CRP (p < 0.000001) and alkaline phosphatase (p < 0.000001). There were also significant negative correlations between calprotectin and ApoA1 and direct HDL-cholesterol.

Conclusions

The reference interval for serum-calprotectin for all study subjects was 0.3–2.6 mg/L. Leukocyte alkaline phosphatase contributes to serum alkaline phosphatase levels.     

Role of faecal calprotectin as non-invasive marker of intestinal inflammation

BACKGROUND/AIM: Faecal calprotectin, a neutrophil granulocyte cytosol protein, is considered a promising marker of intestinal inflammation. We assessed and compared the faecal calprotectin concentration in patients with organic and functional chronic intestinal disorders. PATIENTS AND METHODS: The study was carried out, using a commercially available ELISA test, measuring calprotectin in stool samples collected from 131 patients with inflammatory bowel diseases, 26 with intestinal neoplasms, 48 with irritable bowel syndrome and 34 healthy subjects. RESULTS: Median faecal calprotectin was significantly increased in Crohn's disease (231 microg/g, 95% confidence interval (CI) 110-353 microg/g), ulcerative colitis (167 microg/g, 95% CI 59-276 microg/g), and neoplasms (105 microg/g, 95% CI 0-272 microg/g), whereas normal values were found in patients with irritable bowel syndrome (22 microg/g, 95% CI 9-35 microg/g) and in healthy subjects (11 microg/g, 95% CI 3-18 microg/g). A positive correlation was observed with clinical activity scores in Crohn's disease and ulcerative colitis. In both groups, patients with clinically active disease showed higher calprotectin levels than those observed in patients with quiescent disease (405 microg/g, 95% CI 200-610 microg/g vs. 213 microg/g, 95% CI 85-341 microg/g in CD patients, p<0.05, and 327 microg/g, 95% CI 104-550 microg/g vs. 123 microg/g, 95% CI 40-206 microg/g in UC patients, p<0.001). CONCLUSIONS: Faecal calprotectin appears to be a promising and non-invasive biomarker of intestinal inflammation. If these findings are confirmed, it may provide a useful test for the diagnosis and follow up of inflammatory bowel diseases.     

粪便钙卫蛋白在全消化系统疾病鉴别诊断中的意义

背景：粪便钙卫蛋白（FC）对鉴别诊断肠道炎症性疾病有较高的临床价值,但其在全消化系统疾病中的意义尚不完全清楚。目的：探讨FC在全消化系统疾病鉴别诊断中的意义。方法：纳入2011年6～8月南京军区南京总医院溃疡性结肠炎、克罗恩病、结肠息肉、肠易激综合征、食管炎、食管息肉、慢性胃炎、胃、十二指肠溃疡、急性胰腺炎、胃淋巴瘤患者共47例,以12名健康人作为对照,采用ELISA方法测定FC水平。以受试者工作特征（ROC）曲线分析FC检测的诊断效能。结果：在下消化道疾病中,溃疡性结肠炎和克罗恩病患者的FC水平显著高于结肠息肉和肠易激综合征患者（P〈0．01）．FC检测鉴别这两组疾病的ROC曲线下面积为0．952。食管炎、食管息肉、胃淋巴瘤患者的FC水平显著高于慢性胃炎、胃、十二指肠溃疡、急性胰腺炎患者（P〈0．01）。结论：FC作为一种非侵入性检测方法,对消化系统疾病的鉴别诊断具有一定临床价值。     

粪便生物标记物检测对溃疡性结肠炎的诊断价值研究

目的研究两种粪便生物标记物乳铁蛋白、钙卫蛋白诊断溃疡性结肠炎(ulcerative colitis,UC)活动性的价值。方法选择确诊的UC患者72例作为研究组,60例经结肠镜检查均正常的患者作为对照组,留取结肠镜检查3 d内的粪便样本5~10 g,应用ELISA方法进行粪便乳铁蛋白、钙卫蛋白检测。结果粪便乳铁蛋白、钙卫蛋白水平在缓解组和对照组之间比较差异均无统计学意义(P0.05);活动组分别与缓解组和对照组比较差异均有显著统计学意义(P0.01);活动期各组之间相互比较差异均有统计学意义(P0.01)。粪便乳铁蛋白、钙卫蛋白水平与UC内镜分级标准呈正相关(r=0.873;0.891,P0.01)。结论粪便乳铁蛋白、钙卫蛋白检测能够较准确地诊断UC活动期和缓解期,对临床治疗有指导作用。