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干燥综合征患者腮腺唾液钠水平提示B细胞介导的上皮钠通道破坏。

Parotid salivary sodium levels of Sjögren's syndrome patients suggest B-cell mediated epithelial sodium channel disruption.

作者信息

Pringle Sarah A, Berkhof Bas, van Ginkel Marthe, Liefers Silvia, van der Vegt Bert, Spijkervet Frederik K L, Bootsma Hendrika, Vissink Arjan, Kroese Frans G M

机构信息

Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, The Netherlands.

Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, The Netherlands.

出版信息

Clin Exp Rheumatol. 2021 Nov-Dec;39 Suppl 133(6):30-38. doi: 10.55563/clinexprheumatol/h9hivf. Epub 2021 Oct 14.

DOI:10.55563/clinexprheumatol/h9hivf
PMID:34665704
Abstract

Patients with primary Sjögren's syndrome (SS) suffer widely from lack of saliva production. Here we investigate potential mechanisms underpinning changes in SS patient saliva composition. Sodium concentration was significantly higher in all saliva samples collected: unstimulated submandibular/sublingual (SmSl) saliva (p<0.0001), stimulated SmSl saliva (p=0.002) and stimulated parotid (PG) (p<0.0001) saliva, compared to non-SS sicca controls. Chloride, phosphate and potassium ion concentrations, α-amylase activity and total protein content correlations were less consistently changed between SS and non-SS saliva types. Stimulated PG salivary sodium levels correlated with the degree of CD45+ lymphocytic cell infiltrate in the parotid glands (r=0.69, p<0.001), and even more strongly so with infiltrating CD20+ B cells (r=0.73, p<0.0001). CD3+ T cells were only moderately correlated with salivary sodium (r=0.23, p=0.015). In non-SS control or focus score (FS) negative SS PG tissue, the epithelial sodium channel (ENaC), responsible for sodium transport out of saliva, was localised to the apical membrane of luminal striated duct cells. In PG tissue from FS+ SS patients, apical ENaC expression appeared absent. We hypothesise that B cell-related proinflammatory cytokines in SS salivary glands may dysregulate sodium transport channels in SS.

摘要

原发性干燥综合征(SS)患者普遍存在唾液分泌不足的问题。在此,我们研究了SS患者唾液成分变化的潜在机制。与非SS干燥综合征对照组相比,所采集的所有唾液样本中钠浓度均显著升高:非刺激性颌下腺/舌下腺(SmSl)唾液(p<0.0001)、刺激性SmSl唾液(p=0.002)和刺激性腮腺(PG)唾液(p<0.0001)。SS和非SS唾液类型之间,氯离子、磷酸根离子和钾离子浓度、α淀粉酶活性及总蛋白含量的相关性变化不太一致。刺激性PG唾液钠水平与腮腺中CD45+淋巴细胞浸润程度相关(r=0.69,p<0.001),与浸润的CD20+B细胞的相关性更强(r=0.73,p<0.0001)。CD3+T细胞与唾液钠仅呈中度相关(r=0.23,p=0.015)。在非SS对照组或焦点评分(FS)阴性的SS PG组织中,负责将钠转运出唾液的上皮钠通道(ENaC)定位于管腔纹状管细胞的顶端膜。在FS+SS患者的PG组织中,顶端ENaC表达缺失。我们推测,SS唾液腺中与B细胞相关的促炎细胞因子可能会使SS中的钠转运通道失调。

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