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使用血浆抗 CDTB 和抗微管蛋白水平进行肠易激综合征的第二代生物标志物检测。

Second-Generation Biomarker Testing for Irritable Bowel Syndrome Using Plasma Anti-CdtB and Anti-Vinculin Levels.

机构信息

Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, 8730 Alden Drive, Suite 240E, Los Angeles, CA, 90048, USA.

出版信息

Dig Dis Sci. 2019 Nov;64(11):3115-3121. doi: 10.1007/s10620-019-05684-6. Epub 2019 May 31.

DOI:10.1007/s10620-019-05684-6
PMID:31152332
Abstract

BACKGROUND

ELISA testing for anti-CdtB and anti-vinculin can discriminate patients with irritable bowel syndrome with diarrhea (IBS-D) from those with inflammatory bowel disease (IBD). However, recent findings suggest the antigens can suffer from epitope instability.

AIM

This study aimed to assess effects of incorporating epitope stabilization on test characteristics for distinguishing IBS-D from IBD subjects.

METHODS

Plasma samples from IBS-D subjects from a large-scale clinical trial and subjects with endoscopically active IBD without concurrent immunomodulator therapy were used. After epitope stabilization, CdtB and vinculin were used in ELISA testing. Optical density readings were compared between IBS-D and IBD subjects.

RESULTS

Samples from 100 IBS-D and 31 IBD (22 UC and 9 CD) subjects were tested. IBS-D subjects had higher anti-CdtB titers (P = 0.0001) and higher anti-vinculin titers (P = 0.004) than IBD subjects. The specificities of anti-CdtB and anti-vinculin to differentiate IBS-D from IBD were 93.5% and 90.9%, respectively, with sensitivities of 43.0% and 52.2%, respectively. The positive likelihood ratios of identifying IBS-D with anti-CdtB and anti-vinculin were 6.7 and 5.7, respectively. Assuming a pretest probability of 57% for diagnosis of IBS-D in patients with abdominal pain and change in bowel habits, testing positive for both antibodies resulted in a posttest probability of > 98%.

CONCLUSIONS

Performing epitope stabilization for CdtB and vinculin enhances the test characteristics of ELISAs for anti-CdtB and anti-vinculin in discriminating IBS-D from IBD. Measurement of anti-CdtB and anti-vinculin with this second-generation methodology may further advance our understanding of the role of immunity in functional bowel diseases.

摘要

背景

ELISA 检测抗 CdtB 和抗 vinculin 可区分腹泻型肠易激综合征(IBS-D)患者和炎症性肠病(IBD)患者。然而,最近的研究结果表明,这些抗原可能存在表位不稳定的问题。

目的

本研究旨在评估抗原表位稳定化对区分 IBS-D 和 IBD 患者的检测特征的影响。

方法

使用来自大规模临床试验的 IBS-D 患者和接受内镜检查且无免疫调节剂治疗的 IBD 患者的血浆样本。在进行表位稳定化后,使用 CdtB 和 vinculin 进行 ELISA 检测。比较 IBS-D 和 IBD 患者之间的光密度读数。

结果

共检测了 100 例 IBS-D 和 31 例 IBD(22 例 UC 和 9 例 CD)患者的样本。IBS-D 患者的抗 CdtB 滴度(P=0.0001)和抗 vinculin 滴度(P=0.004)均高于 IBD 患者。抗 CdtB 和抗 vinculin 区分 IBS-D 和 IBD 的特异性分别为 93.5%和 90.9%,敏感性分别为 43.0%和 52.2%。用抗 CdtB 和抗 vinculin 识别 IBS-D 的阳性似然比分别为 6.7 和 5.7。假设腹痛和排便习惯改变的 IBS-D 患者的术前诊断概率为 57%,则两种抗体均为阳性的术后诊断概率>98%。

结论

对 CdtB 和 vinculin 进行表位稳定化可提高 ELISA 检测抗 CdtB 和抗 vinculin 区分 IBS-D 和 IBD 的检测特征。使用这种第二代方法测量抗 CdtB 和抗 vinculin 可能会进一步加深我们对免疫在功能性肠病中作用的理解。

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BMC Gastroenterol. 2024 Dec 3;24(1):448. doi: 10.1186/s12876-024-03509-z.
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Front Physiol. 2024 Mar 5;15:1359003. doi: 10.3389/fphys.2024.1359003. eCollection 2024.
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