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

在我们之前的研究中，我们证实了NP狼疮患者血清（14例患者中的7例）和脑脊液（2例患者中的1例）中存在抗三磷酸异构酶（抗tpi）的IgG抗体。此外，抗tpi抗体指数在NP- sle患者中具有高特异性（94.5%），我们得出结论，抗tpi抗体指数是临床上有用的NP-狼疮标志物（Watanabe et al., 2004）。然而，抗tpi在NP狼疮发病机制中的作用尚不清楚。为了确定抗TPI在NP狼疮发病中的作用，我们1)用抗TPI的Western blotting方法分析NP狼疮患者CSF， 2)从NP狼疮患者CSF中分离IC，观察IC中是否含有TPI， 3)测定NP狼疮患者CSF中抗TPI阳性和阴性的C3d指数，研究补体活化是否与NP狼疮CSF中抗TPI的存在有关。应用免疫印迹法检测12例神经精神性狼疮患者中5例（41.6%）脑脊液中抗三磷酸异构酶抗体（anti-TPI）。抗tpi阳性患者脑脊液C3d指数（n=5，中位数0.446）显著高于抗tpi阴性患者脑脊液C3d指数（n=7，中位数0.098）（p=0.019）。2例抗TPI阳性患者中2例从CSF分离的免疫复合物（IC）中检测到TPI， 5例抗TPI阴性患者中5例从IC中未检测到TPI。我们的研究结果表明，抗tpi在CSF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机制。

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.