Kakalacheva Kristina, Regenass Stephan, Wiesmayr Silke, Azzi Tarik, Berger Christoph, Dale Russell C, Brilot Fabienne, Münz Christian, Rostasy Kevin, Nadal David, Lünemann Jan D
Institute of Experimental Immunology, Laboratory of Neuroinflammation, University of Zürich, 8057 Zürich, Switzerland.
Department of Clinical Immunology, University Hospital Zürich, 8091 Zürich, Switzerland.
Viruses. 2016 Feb 12;8(2):51. doi: 10.3390/v8020051.
A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG) using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects. We detected frequent immunoglobulin M (IgM) reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77%) but rarely in control subjects (2/23; 9%). IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS), were detectable in 7/35 (20%) patients with IM but not in control subjects. Normalization of anti-vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%), even after normalization to increased total IgG levels. Vimentin-specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms. We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM.
传染性单核细胞增多症(IM)是由爱泼斯坦-巴尔病毒引起的有症状的原发性感染,与自身免疫性疾病的发生有关,并增加了患多发性硬化症的风险。在此,我们假设IM期间的免疫激活会触发自身反应性免疫反应。我们使用基于人喉癌上皮细胞(HEp-2)的间接免疫荧光测定法测定了35例IM患者和23例对照受试者针对细胞抗原的抗体反应,并使用基于流式细胞术的测定法测定了针对天然髓鞘少突胶质细胞糖蛋白(MOG)的抗体反应。我们在IM患者中检测到对波形蛋白(中间丝蛋白家族的主要成分)的免疫球蛋白M(IgM)反应频繁(27/35;77%),而在对照受试者中很少见(2/23;9%)。两组中均未检测到与HEp-2细胞结合的IgG自身抗体。相比之下,在高达40%的中枢神经系统(CNS)炎性脱髓鞘疾病儿童中存在的针对天然MOG的IgG反应,在7/35(20%)的IM患者中可检测到,而在对照受试者中未检测到。将IM期间抗波形蛋白IgM水平与总IgM浓度升高进行归一化处理后,抗波形蛋白IgM滴度的显著差异消失。即使在将总IgG水平升高进行归一化处理后,35例IM患者中的3例(9%)仍可检测到抗MOG特异性IgG反应。急性IM症状临床缓解后,波形蛋白特异性IgM和MOG特异性IgG反应降低。我们从数据中得出结论,在部分IM患者中,MOG特异性记忆B细胞被激活。