系统性红斑狼疮(SLE)和系统性硬化症(SSc)的早期诊断和治疗对临床医生提出了重大挑战。尽管各种研究已经观察到健康供体和自身免疫性疾病患者之间的血清选择素水平的变化,包括SLE和SSc,它们作为生物标志物的潜力尚未得到彻底探索.我们旨在研究PSGL-1(sPSGL-1)的血清谱,ADAM8(sADAM8)和P-,E-和L-选择素(sP-,sE-和sL-选择素)在定义的SLE和SSc患者队列中鉴定疾病相关的分子模式。
■我们收集了64名SLE患者的血液样本,58例SSc患者,和81名健康捐献者(HD)。通过ELISA分析sPSGL-1,sADAM8和选择素的水平,并通过流式细胞术分析L-选择素和ADAM8的白细胞膜表达。
■与HD相比,SLE和SSc患者表现出升高的sE-选择素和降低的sL-选择素水平。此外,SLE患者表现出升高的sPSGL-1和sADAM8水平。与SSc相比,SLE患者sL-选择素降低,sADAM8水平升高。此外,SLE和SSc白细胞中L-选择素膜表达低于HD白细胞,与SSc中性粒细胞相比,SLE中性粒细胞中ADAM8膜表达较低。这些改变与每种疾病的一些临床特征有关。使用逻辑回归分析,SLE中的sL-选择素/sADAM8比值,SSc中sL-选择素/sE-选择素和sE-选择素/sPSGL-1比率的组合被鉴定并交叉验证为潜在的血清标志物,以区分这些患者与HD。与每种疾病的可用诊断生物标志物相比,SLE的sL-选择素/sADAM8比值和SSc的联合比值均提供了更高的敏感性(98%SLE和67%SSc正确分类的患者).重要的是,sADAM8/%ADAM8(+)中性粒细胞比率区分SSc和SLE患者,其敏感性和特异性与当前疾病特异性生物标志物相同.
■SLE和SSc呈现sPSGL-1,sE-,sL-选择素,sADAM8和中性粒细胞膜表达可能与它们的发病机制有关,并可能有助于它们的早期诊断。
UNASSIGNED: Early diagnosis and treatment of Systemic lupus erythematosus (SLE) and Systemic sclerosis (SSc) present significant challenges for clinicians. Although various studies have observed changes in serum levels of
selectins between healthy donors and patients with autoimmune diseases, including SLE and SSc, their potential as biomarkers has not been thoroughly explored. We aimed to investigate serum profiles of PSGL-1 (sPSGL-1), ADAM8 (sADAM8) and P-, E- and L-
selectins (sP-, sE- and sL-
selectins) in defined SLE and SSc patient cohorts to identify disease-associated molecular patterns.
UNASSIGNED: We collected blood samples from 64 SLE patients, 58 SSc patients, and 81 healthy donors (HD). Levels of sPSGL-1, sADAM8 and
selectins were analyzed by ELISA and leukocyte membrane expression of L-selectin and ADAM8 by flow cytometry.
UNASSIGNED: Compared to HD, SLE and SSc patients exhibited elevated sE-selectin and reduced sL-selectin levels. Additionally, SLE patients exhibited elevated sPSGL-1 and sADAM8 levels. Compared to SSc, SLE patients had decreased sL-selectin and increased sADAM8 levels. Furthermore, L-selectin membrane expression was lower in SLE and SSc leukocytes than in HD leukocytes, and ADAM8 membrane expression was lower in SLE neutrophils compared to SSc neutrophils. These alterations associated with some clinical characteristics of each disease. Using logistic regression analysis, the sL-selectin/sADAM8 ratio in SLE, and a combination of sL-selectin/sE-selectin and sE-selectin/sPSGL-1 ratios in SSc were identified and cross-validated as potential serum markers to discriminate these patients from HD. Compared to available diagnostic biomarkers for each disease, both sL-selectin/sADAM8 ratio for SLE and combined ratios for SSc provided higher sensitivity (98% SLE and and 67% SSc correctly classified patients). Importantly, the sADAM8/% ADAM8(+) neutrophils ratio discriminated between SSc and SLE patients with the same sensitivity and specificity than current disease-specific biomarkers.
UNASSIGNED: SLE and SSc present specific profiles of sPSGL-1, sE-, sL-
selectins, sADAM8 and neutrophil membrane expression which are potentially relevant to their pathogenesis and might aid in their early diagnosis.