Increased expression of CXCL10 and CCL3 salivary gland chemokines in primary Sjögren's syndrome detected and systematically quantified using novel RNAscope® in situ hybridisation.

IF 3.4 3区 医学 Q3 IMMUNOLOGY
Hanne Borge, Ingrid Beate Ringstad, Lara A Aqrawi, Siren Fromreide, Harsh Nitin Dongre, Hilde Kanli Galtung, Janicke Liaaen Jensen, Kathrine Skarstein
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Abstract

Primary Sjogren's syndrome is a chronic inflammatory disease characterised by the destruction of exocrine glands. We have previously shown significantly upregulated levels of CXCL10 and CCL3 chemokines in saliva from Sjogren's syndrome patients. In this study, we examined the expression pattern and localisation of these chemokines at the site of inflammation in patients' minor salivary glands using novel RNAscope® in situ hybridisation. Minor salivary glands from 33 primary Sjogren's syndrome patients and 22 non-Sjogren's syndrome sicca controls were included. The biopsies were formalin- fixed, paraffin-embedded and histopathologically evaluated. The CXCL10 and CCL3 mRNA expression in the glandular tissue was investigated using reverse transcription quantitative real-time polymerase chain reaction followed by RNAscope® in situ hybridisation. The mRNA expression of CXCL10 was higher than CCL3 in all patients. Significantly elevated expression of CXCL10 and CCL3 was detected in patients that also expressed autoantibody positivity and a positive biopsy for mononuclear cell infiltrates when compared to controls. CXCL10 was localised as clusters within focal infiltrates as well as adjacent to acinar and ductal epithelium, while CCL3 was expressed as scattered single mRNA molecules in focal infiltrates and in acinar cells. Our findings suggest CXCL10 as a possible disease biomarker in primary Sjogren's syndrome due to its upregulated expression in both saliva and minor salivary glands of patients and the localisation in the tissue. This should be re-assessed in a larger primary Sjogren's syndrome patient cohort, followed by additional functional studies to further validate its potential as a disease biomarker.

利用新型 RNAscope® 原位杂交技术检测并系统量化原发性斯约格伦综合征患者唾液腺趋化因子 CXCL10 和 CCL3 的表达。
原发性斯尤金综合征是一种以外分泌腺体破坏为特征的慢性炎症性疾病。我们以前曾发现,在斯尤金综合征患者的唾液中,CXCL10 和 CCL3 趋化因子的水平明显上调。在本研究中,我们使用新型 RNAscope® 原位杂交技术检测了这些趋化因子在患者小唾液腺炎症部位的表达模式和定位。研究对象包括 33 名原发性 Sjogren's 综合征患者的小唾液腺和 22 名非 Sjogren's 综合征筛查对照者的小唾液腺。活检组织经福尔马林固定、石蜡包埋和组织病理学评估。采用反转录定量实时聚合酶链反应和 RNAscope® 原位杂交法检测腺体组织中 CXCL10 和 CCL3 mRNA 的表达。在所有患者中,CXCL10 的 mRNA 表达均高于 CCL3。与对照组相比,在自身抗体阳性和活检单核细胞浸润阳性的患者中,CXCL10 和 CCL3 的表达明显升高。CXCL10 在局灶性浸润中以及毗邻尖状上皮和导管上皮的部位呈集群分布,而 CCL3 则在局灶性浸润和尖状上皮细胞中以分散的单个 mRNA 分子形式表达。我们的研究结果表明,由于 CXCL10 在患者唾液和小唾液腺中的表达上调以及在组织中的定位,它可能是原发性 Sjogren's 综合征的疾病生物标记物。应该在更大的原发性斯约格伦综合征患者群中重新评估这一结果,然后进行更多的功能研究,以进一步验证其作为疾病生物标志物的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.40
自引率
2.20%
发文量
101
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice. The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.
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