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唾液腺分泌组:原发性干燥综合征和非自身免疫性干燥患者分子分层的新工具

Salivary gland secretome: a novel tool towards molecular stratification of patients with primary Sjögren's syndrome and non-autoimmune sicca.

机构信息

Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

出版信息

RMD Open. 2019 Jan 11;5(1):e000772. doi: 10.1136/rmdopen-2018-000772. eCollection 2019.

Abstract

OBJECTIVE

To explore the potential of salivary gland biopsy supernatants (the secretome) as a novel tool to aid in stratification of patients with sicca syndrome and to study local immunopathology in Sjögren's syndrome.

METHODS

Labial salivary gland biopsies were incubated in saline for 1 hour. In these tissue supernatants from a discovery cohort (n=16) of patients with primary Sjögren's syndrome (pSS) and non-Sjögren's sicca (nSS), 101 inflammatory mediators were measured by Luminex. Results were validated in a replication cohort (n=57) encompassing patients with pSS, incomplete SS and nSS.

RESULTS

The levels of 23 cytokines were significantly increased in patients with pSS versus nSS in the discovery cohort. These 23 and 3 additional cytokines were measured in a second cohort. Elevated concentrations of 11 cytokines were validated and the majority correlated with clinical parameters. Classification tree analysis indicated that the concentrations of CXCL13, IL-21, sIL-2R and sIL-7Rα could be used to classify 95.8% of patients with pSS correctly.

CONCLUSION

Labial salivary gland secretomes can be used to reliably assess mediators involved in immunopathology of patients with pSS, potentially contributing to patient classification. As such, this method represents a novel tool to identify therapeutic targets and markers for diagnosis, prognosis and treatment response.

摘要

目的

探索唾液腺活检上清液(分泌组)作为一种辅助干燥综合征患者分层的新工具的潜力,并研究干燥综合征的局部免疫病理学。

方法

将唇腺活检在盐水中孵育 1 小时。在原发性干燥综合征(pSS)和非干燥综合征(nSS)患者的发现队列(n=16)的这些组织上清液中,通过 Luminex 测量了 101 种炎症介质。在包含 pSS、不完整 SS 和 nSS 患者的复制队列(n=57)中验证了结果。

结果

在发现队列中,pSS 患者的 23 种细胞因子水平明显高于 nSS。在第二个队列中测量了这 23 种和另外 3 种细胞因子。验证了 11 种细胞因子浓度升高,其中大多数与临床参数相关。分类树分析表明,CXCL13、IL-21、sIL-2R 和 sIL-7Rα 的浓度可用于正确分类 95.8%的 pSS 患者。

结论

唇腺分泌液可用于可靠地评估与 pSS 患者免疫病理学相关的介质,可能有助于患者分类。因此,这种方法代表了一种识别治疗靶点和诊断、预后和治疗反应标志物的新工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4837/6340539/e7605839286d/rmdopen-2018-000772f01.jpg

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