HoHsieh Ao, Wang Chin Man, Wu Yeong-Jian Jan, Chen Albert, Chang Ming-I, Chen Ji-Yih
Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China.
Department of Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan, Republic of China.
Arthritis Res Ther. 2017 Mar 21;19(1):65. doi: 10.1186/s13075-017-1268-2.
HCMV phosphoprotein 65 (HCMVpp65) is a putative immunogen that acts as an accelerator, inducing autoantibody and exacerbating autoimmune response in susceptible animals. The immunity to pp65 instigates autoimmunity, suggesting that pp65 contains crucial B cell epitope(s) for the development of nephritis. This study narrowed down the target epitope to pp65 for immunization of BALB/c mice and mapping of B cell epitope.
The target epitope pp65 reactivity and B cell epitope mapping was examined in serum from pp65-immunized mice and patients with systemic lupus erythematosus (SLE). Kidney tissue from immunized mice was examined for signs of immune complex nephritis.
Anti-pp65 antibody in serum either from patients with SLE or from pp65-immunized mice exhibited cross-reactivity to several nuclear components such as double-stranded DNA (dsDNA). Moreover, the pp65-immunized mice developed initial signs of glomerulonephritis such as deposition of immunoglobulin G/M (IgG/IgM) and third complement component (C3). With B cell epitope mapping by pp65-derived decapeptides, one dominant epitope, pp65, was identified in serum from pp65-immunized mice and patients with SLE with anti-pp65 antibody. Epitope spreading from pp65 to pp65 was found in pp65-immunized mice in which we generated monoclonal antibodies to pp65 and pp65. However, dsDNA positive reactivity was exclusively observed in Crithidia luciliae stains with pp65-reactive monoclonal antibody. Additionally, we observed the amelioration of autoimmunity following the elevation of IgM targeting pp65 CONCLUSIONS: Our data suggest that pp65 may be an autoimmune or lupus-prone B cell epitope and may catalyze further epitope spreading for inducing autoantibodies in lupus-susceptible individuals.
人巨细胞病毒磷蛋白65（HCMV pp65）是一种假定的免疫原，在易感动物中作为一种促进剂，诱导自身抗体并加剧自身免疫反应。对pp65的免疫引发自身免疫，这表明pp65含有对肾炎发展至关重要的B细胞表位。本研究将靶表位缩小至pp65，用于免疫BALB/c小鼠并绘制B细胞表位图谱。
检测pp65免疫小鼠和系统性红斑狼疮（SLE）患者血清中靶表位pp65的反应性及B细胞表位图谱。检查免疫小鼠的肾组织是否有免疫复合物性肾炎的迹象。
SLE患者或pp65免疫小鼠血清中的抗pp65抗体与几种核成分如双链DNA（dsDNA）表现出交叉反应性。此外，pp65免疫小鼠出现了肾小球肾炎的初始迹象，如免疫球蛋白G/M（IgG/IgM）和第三补体成分（C3）的沉积。通过pp65衍生的十肽进行B细胞表位图谱分析，在pp65免疫小鼠和有抗pp65抗体的SLE患者血清中鉴定出一个主要表位pp65。在我们针对pp65和pp‘65产生单克隆抗体的pp65免疫小鼠中发现了表位从pp65扩展到pp‘65的现象。然而，仅在用pp65反应性单克隆抗体处理的亮绿蝇短膜虫染色中观察到dsDNA阳性反应性。此外，我们观察到靶向pp65的IgM升高后自身免疫得到改善。
我们的数据表明，pp65可能是一个自身免疫或狼疮易感的B细胞表位，可能催化进一步的表位扩展，从而在狼疮易感个体中诱导自身抗体。
