Arbuckle M R, Reichlin M, Harley J B, James J A
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Scand J Immunol. 1999 Nov;50(5):447-55. doi: 10.1046/j.1365-3083.1999.00640.x.
Many aspects of the immune maturation are uncharted. For ordinary human autoimmune systems there are no complete descriptions of the progression from an initial antigenic epitope to a maximally complex immune response. In this study we have exploited a large serial collection of human sera to investigate the development of the anti-Sm autoimmune response in systemic lupus erythematosus (SLE). The results suggest a similar, if not virtually identical, stepwise progression in the early humoral immune maturation of anti-Sm. The amino acid sequence PPPGMRPP comprises the first epitope in the anti-Sm B/B'response and its close relative, PPPGMRGP, the second. Epitopes are subsequently enlarged by the incorporation of neighbouring amino acids. The third and fourth epitopes are also recognised by an antibody in a nearly identical sequence in different lupus patients. A column absorption with PPPGMRPP demonstrates that the epitope spreading among the first four early epitopes appears to occur by the sequential generation of cross-reactive antibodies. Unexpectedly, epitope spreading in this system occurs in a predictable fashion by involving essentially the same sequence of antigenic structures from person to person. In addition, these data support the lupus anti-Sm antibodies originating against a single antigenic structure and, hence, strongly support a unifying mechanism in the generation of these autoantibodies.
免疫成熟的许多方面尚不清楚。对于普通人类自身免疫系统，从初始抗原表位到最大程度复杂免疫反应的进展尚无完整描述。在本研究中，我们利用大量连续收集的人血清来研究系统性红斑狼疮（SLE）中抗Sm自身免疫反应的发展。结果表明，抗Sm早期体液免疫成熟过程中存在相似（如果不是几乎相同）的逐步进展。氨基酸序列PPPGMRPP是抗Sm B/B'反应中的第一个表位，其近亲PPPGMRGP是第二个表位。随后，通过并入相邻氨基酸，表位得以扩大。不同狼疮患者中，第三个和第四个表位也被抗体以几乎相同的序列识别。用PPPGMRPP进行柱吸收表明，前四个早期表位之间的表位扩展似乎是通过交叉反应抗体的顺序产生而发生的。出乎意料的是，该系统中的表位扩展以可预测的方式发生，人与人之间涉及基本相同的抗原结构序列。此外，这些数据支持狼疮抗Sm抗体源自单一抗原结构，因此，有力地支持了这些自身抗体产生的统一机制。
