Kalsi J K, Ravirajan C T, Wiloch-Winska H, Blanco F, Longhurst C M, Williams W, Chapman C, Hillson J, Youniou P, Latchman D
Department of Rheumatology Research, Bloomsbury Rheumatology Unit, London, UK.
Lupus. 1995 Oct;4(5):375-89. doi: 10.1177/096120339500400508.
We have identified and characterised three new idiotypes on human IgM McAbs generated from the splenocytes of a SLE patient with active disease. RT-6, which binds H1 and Sm/RNP, expresses essentially a private Id. Its expression is limited to a small number of human McAbs and the sera from patients with infectious diseases. In contrast RT-72Id and RT-84Id, expressed on McAbs which are polyreactive for two or more antigens, have a public distribution. RT-72Id and RT-84Id are found on McAbs from murine and human adult, and foetal tissues. In sera, significant numbers of SLE, RA and patients with other autoimmune diseases are positive for both Ids. RT-84Id is also elevated in SLE relatives and spouses, and in patients with Klebsiella infection. No correlation with disease activity, IgM or IgG levels was observed with either Id. However, RT-72Id was significantly associated with anti-ssDNA antibodies and RhF. RT-6Id and RT-72Id are located on the framework regions of the mu heavy chain, whereas RT-84Id is present on the kappa light chain, within the binding site. The McAbs are encoded by mainly germline genes: heavy chains of RT-6, RT-72 and RT-84 are encoded by the genes VH26, VH4.22 and VH4.21, respectively, and the light chain sequences of RT-6 and RT-72 are derived from DPL11 and HK102. Immunofluorescent staining revealed the presence of RT-72Id and RT-84Id positive immunoglobulin deposits in 18% and 45%, respectively, of the lupus renal sections compared with none in the disease control group, suggesting that these Ids may contribute to the pathology of the disease.
我们已经鉴定并表征了从一名患有活动性疾病的系统性红斑狼疮（SLE）患者的脾细胞产生的人IgM单克隆抗体（McAbs）上的三种新独特型。RT-6可结合HmH1和Sm/RNP，基本上表达一种个体独特型。其表达仅限于少数人McAbs以及传染病患者的血清。相比之下，在对两种或更多种抗原具有多反应性的McAbs上表达的RT-72Id和RT-84Id具有公共分布。在来自小鼠和人类成年及胎儿组织的McAbs上发现了RT-72Id和RT-84Id。在血清中，大量SLE、类风湿关节炎（RA）患者及其他自身免疫性疾病患者的这两种独特型均呈阳性。RT-84Id在SLE亲属和配偶以及克雷伯菌感染患者中也升高。未观察到任一独特型与疾病活动、IgM或IgG水平之间存在相关性。然而，RT-72Id与抗单链DNA（ssDNA）抗体和类风湿因子（RhF）显著相关。RT-6Id和RT-72Id位于μ重链的框架区，而RT-84Id存在于κ轻链的结合位点内。这些McAbs主要由种系基因编码：RT-6、RT-72和RT-84的重链分别由基因VH26、VH4.22和VH4.21编码，RT-6和RT-72的轻链序列分别源自DPL11和HK102。免疫荧光染色显示，狼疮肾切片中分别有18%和45%存在RT-72Id和RT-84Id阳性免疫球蛋白沉积物，而疾病对照组中未发现，这表明这些独特型可能促成了疾病的病理过程。
