Section for Oral Biology and Immunopathology/Oral Medicine & Pathology, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Proteomics Core Facility at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Sci Rep. 2024 Nov 26;14(1):29377. doi: 10.1038/s41598-024-79473-1.
To investigate if salivary O-linked glycans are altered in primary Sjögren's syndrome (pSS), and thus contributing to explain symptoms of oral dryness, and an impaired oral mucosal barrier function leading to changes in microbial metabolism and colonization by both pathogenic and commensal microorganisms and increased prevalence of oral diseases. O-linked oligosaccharides from stimulated whole saliva (SWS) samples from 24 patients with pSS, 38 patients with non-pSS sicca, and 23 healthy controls were analyzed using liquid chromatography mass spectrometer (LC-MS). Non-fractionated reduced and alkylated saliva was dot-blotted to PVDF-membrane and O-linked oligosaccharides were released using reductive beta-elimination. The 50 most abundant glycans were identified and their intensity compared for each sample, reflecting the relative abundance of individual monosaccharide residues. Comparison of the compositions of O-glycans in SWS samples revealed higher relative levels of sialic acid (NeuAc) and lower levels of neutral amino-monosaccharides (HexNAc) in pSS and non-pSS sicca patients than in the healthy controls. MS fragmentation analysis of salivary O-glycans suggests that altered sulfation, fucosylation, sialylation and distribution of core types may all contribute to the observed alteration, directly or indirectly. Additionally, the short disaccharide sialyl-Tn was most abundant in the saliva samples from patients with pSS. Our findings indicate that the salivary mucin-type O-glycan profile is altered in pSS, reflecting a dysfunction of the post-translational modification of salivary mucins leading to rheological changes of saliva, oral dryness symptoms, and impaired oral mucosal barrier function. The pathophysiological significance of the aberrant O-glycosylation needs further elucidation.
为了探究唾液 O-连接糖链是否在原发性干燥综合征（pSS）中发生改变，并由此解释口腔干燥症状的发生，以及口腔黏膜屏障功能受损导致微生物代谢改变和致病性及共生微生物定植、口腔疾病患病率增加的原因。我们采用液相色谱-质谱联用（LC-MS）技术分析了 24 例 pSS 患者、38 例非 pSS 干燥患者和 23 例健康对照者的刺激全唾液（SWS）样本中的 O-连接寡糖。非分级还原和烷基化唾液被点样到 PVDF 膜上，并用还原β消除法释放 O-连接糖链。鉴定了 50 种最丰富的聚糖，并对每种样本的强度进行了比较，反映了各个单糖残基的相对丰度。SWS 样本中 O-聚糖组成的比较显示，pSS 和非 pSS 干燥患者的唾液中唾液酸（NeuAc）相对水平较高，而中性氨基酸单糖（HexNAc）水平较低。唾液 O-聚糖的 MS 碎裂分析表明，改变的硫酸化、岩藻糖基化、唾液酸化和核心类型分布都可能直接或间接地导致观察到的改变。此外，短二糖唾液酰-Tn 在 pSS 患者的唾液样本中最为丰富。我们的研究结果表明，pSS 患者的唾液黏蛋白型 O-聚糖谱发生改变，反映了唾液黏蛋白翻译后修饰功能障碍，导致唾液流变性改变、口腔干燥症状和口腔黏膜屏障功能受损。异常 O-糖基化的病理生理学意义需要进一步阐明。
