Pathogenicity of anti triose-phosphate isomerase antibody in patients with CNS lupus.

在我们以前的研究中，我们证实了在14例NP狼疮患者的血清(7例)和脑脊液(1例)中存在磷酸丙糖异构酶(抗TPI)的抗体。此外，抗TPI抗体指数在NP-SLE患者中具有很高的特异性(94.5%)，我们得出结论，抗TPI抗体指数是NP狼疮的一个临床有用的标志物(Watanabe等人，2004年)。然而，抗TPI在NP狼疮发病机制中的作用尚不清楚。为探讨抗TPI抗体在NP狼疮发病机制中的作用，1)用抗TPI抗体对NP狼疮患者的脑脊液进行免疫印迹分析，2)从NP狼疮患者的脑脊液中提取IC并检测其是否含有TPI，3)测定抗TPI抗体阳性和阴性的NP狼疮患者脑脊液中的C3d指数，并探讨补体激活与抗TPI抗体的存在是否相关。抗TPI阳性患者(n=5，中位数0.446)的C3d指数显著高于抗TPI阴性患者(n=7，中位数0.098)(P=0.019)。在2例抗TPI阳性患者中，2例从脑脊液分离的免疫复合物(IC)中检测到TPI，在5例抗TPI阴性患者中，5例IC中未检测到TPI。我们的结果提示，抗TPI在脑脊液中形成IC，并通过激活补体系统参与神经精神性狼疮的发病。

In our previous study, we demonstrated the presence of IgG antibodies to triosephosphate isomerase (anti-TPI) in sera (7 of 14 patients) and in CSF (1 of 2 patients) in patients with NP lupus. Furthermore, anti-TPI antibody index has high specificity (94.5%) in patients with NP-SLE, and we concluded that anti-TPI antibody index is a clinically useful marker for NP lupus (Watanabe et al., 2004). However, the role of anti-TPI on NP lupus pathogenesis is not clear. To determine the role of anti-TPI on NP lupus pathogenesis we 1) analyzed CSF of NP lupus patients by Western blotting with anti-TPI, 2) isolated IC from CSF of NP lupus patients and investigated whether the IC contain TPI, and 3) determined C3d index in anti-TPI-positive and negative CSF of NP lupus patients and investigated whether complement activation is associated with the existence of anti-TPI in CSF of NP lupus.We detected anti-triosephosphate isomerase antibodies (anti-TPI) in cerebrospinal fluid (CSF) in 5 of 12 neuropsychiatric lupus patients (41.6%) by Western blotting. C3d index was significantly higher in anti-TPI-positive patient (n=5, median 0.446) than in anti-TPI-negative patient (n=7, median 0.098) (p=0.019) CSF samples. TPI was detected from immune complexes (IC) isolated from CSF in 2 of 2 anti-TPI-positive patients tested and was not detected from IC in 5 of 5 anti-TPI-negative patients tested. Our results suggest that anti-TPI form IC in CSF and contribute to the pathogenesis of neuropsychiatric lupus by activating the complement system.