Vojdani A, Vojdani E, Cooper E
Immunosciences Lab., Inc., Beverly Hills Facility [corrected] USA.
J Intern Med. 2003 Oct;254(4):363-74. doi: 10.1046/j.1365-2796.2003.01203.x.
To measure neurone-specific humoral and cellular immune parameters in MRI-positive patients with multiple sclerosis (MS).
It has been postulated from animal models for MS and in situ evidence in MS patients that antibodies, activated T cells and proinflammatory cytokines are involved in the destruction of myelin sheaths and loss of oligodendrocytes in active areas.
Blood samples were obtained from 20 healthy control subjects and 20 patients with abnormal MRI and clinical diagnosis of MS. Sera were tested for levels of IgG, IgM and IgA against myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) peptides, and a small heat-shock protein, alpha-beta-crystallin. Lymphocytes were isolated and cultured in the presence or absence of MBP, MOG peptides and alpha-beta-crystallin, measured for stimulated T cells, cytokine production and compared with controls.
Patients with MS showed the highest levels of IgG, IgM or IgA antibodies against one or all three tested antigens. Moreover, in the presence of MBP, MOG peptides or alpha-beta-crystallin, a significant percent- age of lymphocytes from MS patients underwent blast transformation, which resulted in high levels of interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha) and tumour necrosis factor beta (TNF-beta) production. Sensitivity of these assays was 60-80% and specificity, 65-70%.
Detection of antibodies against MBP, MOG peptides, alpha-beta-crystallin, lymphocyte stimulation and production of proinflammatory cytokines in response to these antigens could be used as surrogate markers for the confirmation of MS diagnosis. A combination of antibodies, lymphocyte activation or cytokine production with abnormal MRI may significantly increase the sensitivity and specificity of MS diagnosis.
测定MRI呈阳性的多发性硬化症（MS）患者的神经元特异性体液免疫和细胞免疫参数。
从MS的动物模型以及MS患者的原位证据推测，抗体、活化的T细胞和促炎细胞因子参与了活动区域髓鞘的破坏和少突胶质细胞的丢失。
采集20名健康对照者和20名MRI异常且临床诊断为MS的患者的血样。检测血清中针对髓鞘碱性蛋白（MBP）、髓鞘少突胶质细胞糖蛋白（MOG）肽段以及一种小分子热休克蛋白α-β晶状体蛋白的IgG、IgM和IgA水平。分离淋巴细胞，在有或无MBP、MOG肽段和α-β晶状体蛋白存在的情况下进行培养，检测刺激后的T细胞、细胞因子产生情况，并与对照组进行比较。
MS患者针对一种或所有三种检测抗原的IgG、IgM或IgA抗体水平最高。此外，在有MBP、MOG肽段或α-β晶状体蛋白存在时，MS患者的淋巴细胞中有相当比例发生了母细胞转化，导致高水平的γ干扰素（IFN-γ）、肿瘤坏死因子α（TNF-α）和肿瘤坏死因子β（TNF-β）产生。这些检测方法的敏感性为60 - 80%，特异性为65 - 70%。
检测针对MBP、MOG肽段、α-β晶状体蛋白的抗体、淋巴细胞刺激以及对这些抗原产生的促炎细胞因子，可作为确诊MS的替代标志物。抗体、淋巴细胞活化或细胞因子产生与MRI异常相结合，可能会显著提高MS诊断的敏感性和特异性。
