CAJ | 학술논문

目的从系统生物学角度全面研究弥漫增生型狼疮肾炎(Ⅳ型LN)和膜型狼疮肾炎(Ⅴ型LN)患者血清细胞因子表达谱.方法分离静脉血清,通过抗体芯片技术同时检测4种Th1和5种Th2细胞因子表达.结果 ①细胞因子表达谱:在检测的9种细胞因子中,Ⅳ型LN患者有7种明显升高,包括3种Th1细胞因子[干扰素(INF)-γ、白细胞介素(IL)-2、肿瘤坏死因子(TNF)-α)]和4种Th2细胞因子(IL-4、IL-6、IL-10、IL-13);而Ⅴ型LN仅有4种细胞因子表达上调(IL-2、IL-4、IL-10和IL-13).②相关性分析:Ⅳ型LN患者细胞因子与临床表现之间相关性较强,如IL-5与抗dsDNA抗体滴度及血肌酐呈正相关、与C3呈负相关;IL-10与系统性红斑狼疮(SLE)疾病活动指数(SLEDA1)呈正相关、与尿蛋白及血红蛋白浓度均呈负相关;IL-13与尿蛋白浓度呈负相关,IL-1与SLEDAI呈正相关、与血红蛋白浓度呈负相关.Ⅴ型LN患者仅IL-1与血肌酐之间呈正相关,IL-4与尿蛋白之间呈负相关.结论不同病理分型的LN患者体内细胞因子表达谱不同,提示不同病理分型的LN其内在的免疫学发病机制存在差异,也提示不同的细胞因子表达可能代表不同类型的LN.
목적 종계통생물학각도전면연구미만증생형랑창신염(Ⅳ형LN)화막형랑창신염(Ⅴ형LN)환자혈청세포인자표체보.방법 분리정맥혈청,통과항체심편기술동시검측4충Th1화5충Th2세포인자표체.결과 ①세포인자표체보:재검측적9충세포인자중,Ⅳ형LN환자유7충명현승고,포괄3충Th1세포인자[간우소(INF)-γ、백세포개소(IL)-2、종류배사인자(TNF)-α)]화4충Th2세포인자(IL-4、IL-6、IL-10、IL-13);이Ⅴ형LN부유4충세포인자표체상조(IL-2、IL-4、IL-10화IL-13).②상관성분석:Ⅳ형LN환자세포인자여림상표현지간상관성교강,여IL-5여항dsDNA항체적도급혈기항정정상관、여C3정부상관;IL-10여계통성홍반랑창(SLE)질병활동지수(SLEDA1)정정상관、여뇨단백급혈홍단백농도균정부상관;IL-13여뇨단백농도정부상관,IL-1여SLEDAI정정상관、여혈홍단백농도정부상관.Ⅴ형LN환자부IL-1여혈기항지간정정상관,IL-4여뇨단백지간정부상관.결론 불동병리분형적LN환자체내세포인자표체보불동,제시불동병리분형적LN기내재적면역학발병궤제존재차이,야제시불동적세포인자표체가능대표불동류형적LN.
Objective To obtain a global view of cytokine profile in lupus nephritis (LN), and to co-mpare the pattern of cytokine profile in patients with different renal lesions, primarily diffuse proliferative lupus nephritis (Ⅳ-LN) and membranous lupus nephritis (Ⅴ-LN). Methods Thirtypatients with biopsy proven active LN (class Ⅳ, n=15; class Ⅴ, n=15) and 15 healthy controls were enrolled in this study. Serum conc-entration of Th1 cytokines (IFN-γ, IL-1, IL-2, and TNF-α) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13) were simultaneously analyzed using Fast Quant Human Th1/Th2 protein array. Results ① Cytokine profiling: in patients with class Ⅳ-LN, the levels of most of the detected cytokines elevated marked compared to normal controls, including both Th1 (IL-2, INF-γ and TNF-α) and Th2 (IL-4, IL-6, IL-10 and IL-13) cytokines. Among them, both Th1 (INF-γ and TNF-α) and Th2 (IL-6, IL-10 and IL-13) cytokines were 10 times higher than normal controls. However, patients with class Ⅴ LN demonstrated a different cytokine pro-filing compared to class Ⅳ LN. Only 4 out of 9 cytokines were significantly increased. In addition to IL-2, all of those cytokines produced by Th2 (IL-4, IL-10 and IL-13) as well as IL-10 was 10 times higher than normal controls. The main difference of cytokines between patients with class Ⅳ LN and patients with class Ⅴ LN was among Th1 cytokines (IFN-γ, IL-2 and TNF-α). There was a significant correlation between clinical manifestations and cytokines in class Ⅳ LN, especially among Th2 cytokine. There was positive correlation between IL-5 and anti-dsDNA titer(r=0.708, P<0.05), IL-5 and creatinin(r=0.681, P<0.05) and IL-10 and SLEDAI scores (r=0.877, P<0.0 ). On the other hand, there was also negative correlation between some Th2 cytokines and clinical manifestations. There was negative correlation between IL-5 and complement C3 level (r=-0.643, P<0.05), IL-10 and proteinuria(r=-0.659, P<0.O5), IL-10 and hemoglobin level (r=-0.856, P<0.001), as well as IL-13 and proteinuria (r=-0.769, P<0.05). In addition, IL-1 was positive correlated with SLEDAI, while it was negatively correlated with bemoglobulin level. As for class Ⅴ LN, there was positive correlation between IL-1 and creatinin level (r=0.784, P<0.05), but negative correlation between IL-4 and proteinuria (r=-0.754, P<0.05). Conclusion Patients with class Ⅳ renal lesion have shown a broad changes of cytokine activity, while up-regulation of Th2 cytokines is more predominant in patients with class Ⅴ LN. These suggest that the expression of different cytokines may be associated with different patterns of lupus renal lesions. These findings may shed light on the further exploring of the underlying mechanisms that mediate different patterns of renal lesions, as well as designing a rational therapeutic strategy for the treatment of LN.