Satoh Minoru, Akaogi Jun, Kuroda Yoshiki, Nacionales Dina C, Yoshida Hideo, Yamasaki Yoshioki, Reeves Westley H
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL 32610-0221, USA.
J Rheumatol. 2004 Dec;31(12):2382-9.
Autoantibodies to U1-C have been considered a minor component of anti-snRNP (nRNP, Sm) response based on Western blotting. However, we have previously shown that virtually all human anti-nRNP sera contain antibodies to native U1-C, as well as novel autoantibodies that stabilize the molecular interaction of the U1-C-Sm core particle. The biological significance of stabilizing antibodies was investigated by titering anti-U1-C/U1-A compared to stabilizing antibodies, and by examining the effects of stabilizing antibodies on antigen processing.
Autoantibodies to individual native components of U1snRNP (immunoprecipitation of RNase-treated cell extract) and stabilizing antibodies (dissociation of snRNP on anti-Sm monoclonal antibodies by 1 M MgCl2) in human autoimmune sera were titered. Effects of stabilizing antibodies on proteolysis were assessed by incubating UsnRNP with anti-snRNP/Sm autoimmune sera prior to protease digestion.
Autoantibodies to native U1-C and U1-C-Sm core particle stabilizing antibodies were universally present in human anti-nRNP or anti-nRNP + anti-Sm sera, but not in anti-Sm sera. Antibodies to U1-A were less common. The titers of stabilizing antibodies were higher than those of antibodies to U1-C (p < 0.01), indicating that the stabilizing antibodies were a significant component of the anti-snRNP response. The stabilizing anti-nRNP, but not anti-Sm antibodies, protects the Sm core particle from dissociation and proteolysis.
Autoantibodies stabilizing the U1-C-Sm core particle were universally present in anti-nRNP sera and delay proteolysis of the Sm core particle. They may suppress spreading of the autoimmune response to Sm by delaying or altering processing of the Sm core proteins by antigen-presenting cells.
基于蛋白质印迹法，U1-C自身抗体被认为是抗snRNP（nRNP、Sm）反应的次要成分。然而，我们之前已经表明，几乎所有人类抗nRNP血清都含有针对天然U1-C的抗体，以及能稳定U1-C-Sm核心颗粒分子相互作用的新型自身抗体。通过滴定抗U1-C/U1-A与稳定抗体，并检测稳定抗体对抗原加工的影响，研究了稳定抗体的生物学意义。
对人类自身免疫血清中针对U1snRNP单个天然成分的自身抗体（经核糖核酸酶处理的细胞提取物的免疫沉淀）和稳定抗体（通过1 M MgCl2在抗Sm单克隆抗体上解离snRNP）进行滴定。在蛋白酶消化之前，将U snRNP与抗snRNP/Sm自身免疫血清孵育，评估稳定抗体对蛋白水解的影响。
针对天然U1-C和U1-C-Sm核心颗粒稳定抗体的自身抗体普遍存在于人类抗nRNP或抗nRNP + 抗Sm血清中，但不存在于抗Sm血清中。针对U1-A的抗体较少见。稳定抗体的滴度高于针对U1-C的抗体（p < 0.01），表明稳定抗体是抗snRNP反应的重要组成部分。稳定抗nRNP抗体而非抗Sm抗体可保护Sm核心颗粒免于解离和蛋白水解。
稳定U1-C-Sm核心颗粒的自身抗体普遍存在于抗nRNP血清中，并延迟Sm核心颗粒的蛋白水解。它们可能通过延迟或改变抗原呈递细胞对Sm核心蛋白的加工来抑制自身免疫反应向Sm的扩散。
