Stafford H A, Anderson C J, Blalock D B, Reichlin M
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Clin Exp Rheumatol. 1998 Mar-Apr;16(2):119-24.
Autoantibodies to the ribosomal P phosphoproteins (anti-P) appear almost exclusively in SLE. The mechanism by which these autoantibodies appear is unknown. The aim of this study was to determine if IgM and IgG isotype switching occurs during the development of the anti-P autoantibody response.
Patients who acquired IgG anti-P during clinical observation had their serial serum samples from this period screened for IgM and IgG anti-P by immunoblots and ELISAs. Rabbits were immunized with the immunodominant peptide of the ribosomal P proteins ("P-peptide") cross-linked to bovine serum albumin. Their serial samples were also analyzed for IgM and IgG anti-P before and after repeated immunizations.
Two patients were identified who developed transient low titer IgM anti-P that preceded the development of their IgG anti-P. Both patients were clinically well during their peak of IgM anti-P, and developed flares of disease coincident with their high titered IgG anti-P response. The "P-peptide"-immunized rabbits developed an IgM anti-P response that preceded IgG anti-P, and that decreased over time.
We conclude that IgM to IgG isotype switching occurs in the anti-P autoimmune response. These findings suggest that the autoimmune response to the ribosomal P proteins may be antigen-driven.
核糖体P磷蛋白自身抗体（抗-P）几乎仅出现在系统性红斑狼疮（SLE）中。这些自身抗体出现的机制尚不清楚。本研究的目的是确定在抗-P自身抗体应答的发展过程中是否发生IgM和IgG的同种型转换。
在临床观察期间获得IgG抗-P的患者，对其在此期间的系列血清样本通过免疫印迹法和酶联免疫吸附测定法检测IgM和IgG抗-P。用与牛血清白蛋白交联的核糖体P蛋白的免疫显性肽（“P肽”）免疫兔子。在重复免疫之前和之后，对它们的系列样本也进行IgM和IgG抗-P分析。
鉴定出两名患者，他们在产生IgG抗-P之前出现了短暂的低滴度IgM抗-P。两名患者在IgM抗-P峰值期间临床状况良好，并在高滴度IgG抗-P应答时出现疾病发作。用“P肽”免疫的兔子在产生IgG抗-P之前出现了IgM抗-P应答，并且随着时间的推移而下降。
我们得出结论，在抗-P自身免疫应答中发生了从IgM到IgG的同种型转换。这些发现表明，对核糖体P蛋白的自身免疫应答可能是抗原驱动的。
