Reichlin M
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Lupus. 2003;12(12):916-8. doi: 10.1191/0961203303lu502oa.
Within two years of the recognition of autoantibodies to ribosomal P proteins in patients with systemic lupus erythematosus (SLE) an association with anti-P autoantibodies with psychosis was noted. While there has been some controversy about this association, ample evidence suggests a meaningful relationship between anti-P antibodies and central nervous system (CNS) disease. This evidence consists of 1) seven independent studies showing a strong relationship between anti-P antibodies and CNS disease; 2) longitudinal studies showing fluctuations of anti-P antibodies with episodes of psychosis; 3) correlation of anti-P antibodies with general disease activity; and 4) acid eluates form lupus renal tissue were found to contain anti-P antibodies enriched 30-fold with respect to their specific activity in serum heralding a direct role of anti-P antibodies in disease expression. Finally, there is evidence that the P protein resides on normal cells in an immunologically accessible way and evidence exists that anti-P antibodies are able to bind and penerate cells in culture, and once inside cells can affect a profound inhibition of protein synthesis in living cells. Taken together, these observations provide evidence linking anti-P antibodies to various forms of CNS disease. While this is true, there are other autoantibodies in SLE patients such as anti-dsDNA and antiglial fibrillary protein which may also play a role in the CNS disease of SLE patients. Continued study will inform us of the relative contribution of these autoantibodies to CNS disease in SLE patients.
在系统性红斑狼疮(SLE)患者中识别出针对核糖体P蛋白的自身抗体后的两年内,人们注意到抗P自身抗体与精神病之间存在关联。尽管关于这种关联存在一些争议,但大量证据表明抗P抗体与中枢神经系统(CNS)疾病之间存在有意义的关系。这些证据包括:1)七项独立研究表明抗P抗体与CNS疾病之间存在密切关系;2)纵向研究表明抗P抗体随精神病发作而波动;3)抗P抗体与总体疾病活动的相关性;4)发现狼疮肾组织的酸洗脱液中所含抗P抗体的比活性比血清中高30倍,这预示着抗P抗体在疾病表现中起直接作用。最后,有证据表明P蛋白以免疫可及的方式存在于正常细胞上,并且有证据表明抗P抗体能够在培养物中结合并穿透细胞,一旦进入细胞就可以对活细胞中的蛋白质合成产生深远的抑制作用。综上所述,这些观察结果提供了将抗P抗体与各种形式的CNS疾病联系起来的证据。虽然确实如此,但SLE患者中还有其他自身抗体,如抗双链DNA和抗神经胶质纤维酸性蛋白,它们也可能在SLE患者的CNS疾病中起作用。持续的研究将让我们了解这些自身抗体对SLE患者CNS疾病的相对贡献。