Koffler D, Carr R, Agnello V, Thoburn R, Kunkel H G
J Exp Med. 1971 Jul 1;134(1):294-312. doi: 10.1084/jem.134.1.294.
The specificities of anti-polynucleotide antibodies found in human sera were studied using several immunological procedures. Anti-native DNA (NDNA) antibodies and certain anti-double-stranded RNA (DSRNA) antibodies were found to react with single-stranded DNA (SDNA), and anti-NDNA antibodies were observed to react more avidly with SDNA than with NDNA in most sera tested. Antibodies to NDNA showed no preferential reactivity with NDNA or SDNA derived from mammalian tissue, bacterial, or viral sources. Precipitating antibodies reactive with individual bases, with common determinants of bases, and with common determinants of SDNA and NDNA were detected utilizing synthetic polydeoxyribonucleotides. Antibodies to DSRNA were also heterogeneous and reactive with both Poly A . Poly U and Poly I . Poly C in addition to reactivity with Poly A and SDNA. In contrast, antibodies to a ribonucleo-protein determined by hemagglutination and by precipitation showed no reaction with NDNA, SDNA, or DSRNA. Serial studies of serum specimens from patients with systemic lupus erythematosus (SLE) indicated that anti-NDNA antibodies were closely associated with disease activity. Titers of antibodies to SDNA or DSRNA were also frequently increased during these periods but in addition showed peaks during quiescent periods. Anti-NDNA antibodies were detected in most patients' sera at sometime during the course of the disease. Three patients were observed with active SLE, who did not develop anti-NDNA antibodies, even in the presence of severe renal disease. Evidence that other antigen-antibody systems may also play a role in the pathogenesis of the renal disease was particularly apparent in these patients. Anti-ribonucleoprotein antibodies were not well correlated with the peaks of antibody activity of other polynucleotide antibodies, suggesting that an independent immunogen was responsible for induction of these antibodies. The close association of certain populations of anti-polynucleotide antibodies during the course of active SLE, the presence of cross-reacting antigenic determinants of SDNA, NDNA, and DSRNA, the preferential avidity of anti-NDNA antibodies for SDNA, and the frequent increase of anti-SDNA antibodies in SLE and other diseases associated with active tissue destruction suggest that SDNA is a ubiquitous antigen that may stimulate the formation of antibodies reactive with a variety of polynucleotides.
利用多种免疫学方法研究了人血清中抗多核苷酸抗体的特异性。发现抗天然DNA（NDNA）抗体和某些抗双链RNA（DSRNA）抗体可与单链DNA（SDNA）发生反应，并且在大多数检测的血清中观察到抗NDNA抗体与SDNA的反应比与NDNA的反应更强烈。抗NDNA抗体对源自哺乳动物组织、细菌或病毒来源的NDNA或SDNA没有优先反应性。利用合成多脱氧核糖核苷酸检测到了与单个碱基、碱基的共同决定簇以及SDNA和NDNA的共同决定簇发生反应的沉淀抗体。抗DSRNA抗体也是异质性的，除了与Poly A和SDNA发生反应外，还与Poly A·Poly U和Poly I·Poly C发生反应。相比之下，通过血凝和沉淀确定的核糖核蛋白抗体与NDNA、SDNA或DSRNA无反应。对系统性红斑狼疮（SLE）患者血清标本的系列研究表明，抗NDNA抗体与疾病活动密切相关。在这些时期，抗SDNA或DSRNA抗体的滴度也经常升高，但在静止期也会出现峰值。在大多数患者疾病过程中的某个时间检测到抗NDNA抗体。观察到3例活动性SLE患者，即使存在严重肾病也未产生抗NDNA抗体。在这些患者中，其他抗原-抗体系统也可能在肾病发病机制中起作用的证据尤为明显。抗核糖核蛋白抗体与其他多核苷酸抗体的抗体活性峰值没有很好的相关性，这表明一种独立的免疫原负责诱导这些抗体。在活动性SLE过程中某些抗多核苷酸抗体群体的密切关联、SDNA、NDNA和DSRNA交叉反应抗原决定簇的存在、抗NDNA抗体对SDNA的优先亲和力以及SLE和其他与活跃组织破坏相关疾病中抗SDNA抗体的频繁增加表明，SDNA是一种普遍存在的抗原，可能刺激形成与多种多核苷酸发生反应的抗体。
