Arbuckle M R, Schilling A R, Harley J B, James J A
Arthritis and Immunology Program, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, 73104, USA.
J Autoimmun. 1998 Oct;11(5):431-8. doi: 10.1006/jaut.1998.0227.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of large amounts of characteristic autoantibodies. Anti-Sm and anti-nRNP (also known as anti-spliceosome) autoantibodies are among these. Previous epitope mapping of anti-spliceosomal antibodies has identified multiple antigenic determinants within this complex immune response. In this report we describe an SLE patient with a relatively simple, long-lasting anti-spliceosomal response. In the earliest serum sample tested the autoimmune response appeared restricted to the similar peptides PPPGMR(P,G)P of Sm B/B', PAPGMRPP of nRNP C, and PPPGMIPP of nRNP A. Unlike all the other tested lupus patients with anti-spliceosomal autoantibodies, in this patient these proline-rich epitopes remained the primary target for humoral autoimmunity in subsequent serum samples collected over many years. Absorption of anti-PAPGMRPP antibodies also removed binding to PPPGMR(P,G)P and PPPGMIPP. Isolated antibodies to PAPGMRPP were capable of binding Sm B/B', nRNP C and nRNP A by Western blot. For this particular SLE patient the autoimmune response observed against these three proteins is a single cross-reactive response against a similar proline-rich motif. Also, this patient has failed to undergo the B cell epitope spreading, typically observed in the naturally arising autoimmune response against the spliceosome in human lupus patients.
系统性红斑狼疮（SLE）是一种慢性自身免疫性疾病，其特征是产生大量具有特征性的自身抗体。抗Sm和抗nRNP（也称为抗剪接体）自身抗体就是其中的一部分。先前对抗剪接体抗体的表位作图已在这种复杂的免疫反应中确定了多个抗原决定簇。在本报告中，我们描述了一名具有相对简单、持久的抗剪接体反应的SLE患者。在检测的最早血清样本中，自身免疫反应似乎局限于Sm B/B'的相似肽段PPPGMR(P,G)P、nRNP C的PAPGMRPP和nRNP A的PPPGMIPP。与所有其他检测的具有抗剪接体自身抗体的狼疮患者不同，在该患者中，这些富含脯氨酸的表位在随后多年收集的血清样本中仍然是体液自身免疫的主要靶点。抗PAPGMRPP抗体的吸收也消除了与PPPGMR(P,G)P和PPPGMIPP的结合。通过蛋白质印迹法，分离出的抗PAPGMRPP抗体能够与Sm B/B'、nRNP C和nRNP A结合。对于这位特定的SLE患者，观察到的针对这三种蛋白质的自身免疫反应是针对一个相似的富含脯氨酸基序的单一交叉反应。此外，该患者未发生B细胞表位扩展，而这在人类狼疮患者针对剪接体的自然发生的自身免疫反应中通常会观察到。
