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儿童及青少年多发性硬化症中髓鞘碱性蛋白和髓鞘少突胶质细胞糖蛋白的T细胞库

Myelin basic protein and myelin oligodendrocyte glycoprotein T-cell repertoire in childhood and juvenile multiple sclerosis.

作者信息

Correale Jorge, Tenembaum Silvia N

机构信息

Department of Neurology, Raúl Carrea Institute for Neurological Research, (FLENI), Montañeses 2325 (1428), Buenos Aires, Argentina.

出版信息

Mult Scler. 2006 Aug;12(4):412-20. doi: 10.1191/135248506ms1282oa.

Abstract

Multiple sclerosis (MS) is usually a disease of young adulthood, its clinical onset occurring between 20 and 40 years of age; however, today there is general consensus that MS can also occur in children, adolescents and even in infants. In order to gain further insight into the T-cell repertoire present in this particular group of patients myelin basic protein (MBP)-, MBP exon-2- and myelin oligodendrocyte glycoprotein (MOG)Igd-specific T-cell lines (TCLs) were isolated from 18 patients whose symptoms had started before the age of 16. Epitope specificity was established by measuring proliferative responses, and interferon-y (IFN-y) secretion by using a panel of overlapping synthetic peptides. For MOGIgd, the T-cell response was focused on three main immunodominant epitopes comprising residues 1-26, 36-60 and 63-87. For MBP the predominant immune responses were directed against peptides 83-102, 139-153 and 146-162. When compared to those observed in adult-onset MS patients, anti-MOGIgd specificity and anti-MBP responses showed similar results. Moreover, the number of MBP exon-2 TCLs isolated, and the magnitude of the specific IFN-gamma secretion induced were similar, both in childhood/juvenile-onset and adult-onset MS patients. Thus, despite differences in the clinical and neuroimaging manifestations of MS, these results would seem to indicate that both the spectrum of MBP found, as well as the MOGIgd epitopes recognized by peripheral blood T cells in MS, appear to be similar for childhood/juvenile-onset and adult-onset patients.

摘要

多发性硬化症(MS)通常是一种发生于青壮年时期的疾病,其临床发病年龄在20至40岁之间;然而,如今人们已普遍达成共识,MS也可发生于儿童、青少年甚至婴儿。为了更深入了解这一特殊患者群体中存在的T细胞库,我们从16岁之前出现症状的18名患者中分离出了髓鞘碱性蛋白(MBP)、MBP外显子2和髓鞘少突胶质细胞糖蛋白(MOG)Igd特异性T细胞系(TCLs)。通过测量增殖反应以及使用一组重叠合成肽来检测干扰素-γ(IFN-γ)分泌,确定了表位特异性。对于MOGIgd,T细胞反应集中在三个主要的免疫显性表位,包括第1 - 26位、36 - 60位和63 - 87位残基。对于MBP,主要的免疫反应针对的是第83 - 102位、139 - 153位和146 - 162位肽段。与成年发病的MS患者相比,抗MOGIgd特异性和抗MBP反应显示出相似的结果。此外,在儿童/青少年发病和成年发病的MS患者中,分离出的MBP外显子2 TCLs数量以及诱导产生的特异性IFN-γ分泌量均相似。因此,尽管MS在临床和神经影像学表现上存在差异,但这些结果似乎表明,儿童/青少年发病和成年发病患者中发现的MBP谱以及外周血T细胞识别的MOGIgd表位似乎相似。

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