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抗核抗体阳性的多发性硬化症患者中可溶性Fas和FasL浓度升高。

Elevated Concentrations of Soluble Fas and FasL in Multiple Sclerosis Patients with Antinuclear Antibodies.

作者信息

Sremec Josip, Tomasović Sanja, Tomić Sremec Nada, Šućur Alan, Košćak Lukač Jelena, Bačić Baronica Koraljka, Grčević Danka, Kovačić Nataša

机构信息

Department of Neurology, "Sveti Duh" Clinical Hospital, Sveti Duh 64, 10000 Zagreb, Croatia.

Neurology Clinic, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Sveti Duh 64, 10000 Zagreb, Croatia.

出版信息

J Clin Med. 2020 Nov 26;9(12):3845. doi: 10.3390/jcm9123845.

Abstract

Antinuclear antibodies (ANA) are currently considered as an epiphenomenon of apoptotic processes, possibly in control of autoreactivity in patients with multiple sclerosis (MS). Apoptosis of reactive lymphocytes by the Fas/FasL system is described as an effective control mechanism for autoreactivity in MS. We aimed to provide a context to the potential link between ANA and peripheral lymphocyte apoptosis in MS. The presence of ANA was detected in sera by immunofluorescence assay, and concentrations of sFas and sFasL were determined in the sera of 44 and cerebrospinal fluid (CSF) of 11 relapsing-remitting (RR) MS patients using cytometric bead-based array, and their association with the disease characteristics was determined. ANA were detected in the sera of 43.2% of RRMS patients, and their frequency was the highest in patients with disease duration of less than one year (88,89%). In addition, the number of experienced relapses was lower in ANA-positive patients. Concentrations of sFasL were inversely associated with patients' expanded disability status scale (EDSS) scores. Low concentrations of both soluble factors strongly discriminated patients with moderate to severe disability, from patients with mild or absent disability only in a group of patients with prolonged disease duration (>10 years). Both soluble mediators were significantly higher in ANA-positive patients. FasL concentrations were inversely associated with the number of relapses. There is a potential link between the presence of ANA and peripheral lymphocyte apoptosis mediated by Fas/FasL system in MS, whose precise role and significance needs to be determined by future mechanistic studies.

摘要

抗核抗体(ANA)目前被认为是凋亡过程的一种附带现象,可能参与了多发性硬化症(MS)患者自身反应性的调控。Fas/FasL系统介导的反应性淋巴细胞凋亡被描述为MS中自身反应性的一种有效调控机制。我们旨在探讨ANA与MS患者外周淋巴细胞凋亡之间潜在联系的背景情况。通过免疫荧光法检测血清中ANA的存在,并使用基于细胞计数微球的阵列法测定44例复发缓解型(RR)MS患者血清和11例患者脑脊液(CSF)中sFas和sFasL的浓度,并确定它们与疾病特征的关联。43.2%的RRMS患者血清中检测到ANA,疾病病程小于1年的患者中ANA频率最高(88.89%)。此外,ANA阳性患者的复发次数较少。sFasL浓度与患者的扩展残疾状态量表(EDSS)评分呈负相关。仅在病程较长(>10年)的一组患者中,两种可溶性因子浓度低能强烈区分中度至重度残疾患者与轻度或无残疾患者。两种可溶性介质在ANA阳性患者中均显著升高。FasL浓度与复发次数呈负相关。MS中ANA的存在与Fas/FasL系统介导的外周淋巴细胞凋亡之间存在潜在联系,其确切作用和意义有待未来的机制研究确定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34ba/7761165/a1a94559bffb/jcm-09-03845-g001.jpg

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