系统性红斑狼疮发病机理和临床研究

A STUDIES ON THE PATHOGENESIS AND CLINIC IN SLE

系统性红斑狼疮（ＳＬＥ）是一全身性多器官受累的自身免疫性疾病，发病机理未明。本课题从分子生物学和细胞生物学角度进行研究，发现抗ＤＮＡ免疫复合物（抗ＤＮＡＩＣｓ）与狼疮性肾炎（ＬＮ）发病密切相关，能促系膜细胞产生白介素６（ＩＬ６），对疾病的活动性、疗效判断有一定价值。在细胞因子与ＬＮ的相关性研究中，发现可溶性白介素２受体（ｓＩＬ２Ｒ）、肿瘤坏死因子α（ＴＮＦα）、ＩＬ６及内皮素（ＥＴ）等与ＳＬＥ的活动性明显相关，而且在国内外首次发现巨噬细胞移动抑制因子（ＭＩＦ）与ＳＬＥ活动性及肾损害密切相关。此外，红细胞免疫功能障碍及淋巴细胞凋亡也参与ＬＮ的发病。在临床研究方面，本课题除对ＬＮ进行研究外，对狼疮脑、血液危象及肺胸膜病变等也作了深入研究，并发现ＳＬＥ并发溢乳现象，证明与泌乳素（ＰＲＬ）增高有关；肾活检对ＬＮ的诊断、疗效及预后的评价有重要意义。皮质激素联合环磷酰胺冲击（ＣＴＸＩＶ）是治疗ＬＮ及其它内脏损害的有效的成功的疗法。本课题还研究小剂量环孢素Ａ（ＣｓＡ）治疗ＬＮ，取得良好疗效；静脉输注大剂量免疫球蛋白（ＩＶＩＧ）治疗危重ＳＬＥ是一有效的抢救措施。对ＳＬＥ的预后因素也作了观察和分析。

Systemic Lupus erythematosus (SLE) is an autoimmune disease characterized by multiple system injury. The pathogenesis of SLE has not yet been elucidated. Previously, by using molecular biology and cytobiology method, we have carried out serial studies which showed that DNAantiDNA immune complexes(DNAantiDNA ICs) could enhance interleukin6(IL6) production by mesangial cells and plays an important role in the pathogenesis of lupus nephritis(LN). This suggests that DNAantiDNA ICs may be valuable in the evaluation of disease activity and treatment of LN. The activity of LN was also found to be significantly correlated with soluble interleukin2 receptor (sIL2R), tumor necrosis factorα(TNFα),IL6 and endothelin(ET).We first reported that macrophage migration inhibitory factor (MIF) is associated with renal injury and activity of SLE. We also found that disorder of erythrocyte immune function and the apoptosis of lymphocytes took part in the pathogenesis of LN. In clinical studies,we studied not only LN but also neuropsychiatric lupus, blood crisis, pulmonary and pleural involvement of SLE, SLE with galactorrhea which is showed to be associated with the increased of serum prolactin level. We have shown that renal biopsy has a significant value for the diagnosis, treatment and prognosis of LN. We also shown that combined steroid and intravenous cyclophosphamide pulse therapy(TVCTX) is an effective and successful therapeutic strategy for LN and other organ injury. In other clinical studies we showed that low dose cyclosporin A(CsA) is effective in the treatment of LN and high dose introvenous immunoglobulin (IVIG) is a valuable rescuing measure for severe SLE patients. In addition, we studied and evaluated prognostic factors in SLE.