未经证实:狼疮性肾炎(LN)血栓性微血管病(TMA)的发病机制仍然很复杂。本研究旨在检测补体凝集素途径(LP)和旁路途径(AP)成分在肾组织中的沉积,然后评估LN队列中有或没有TMA患者的临床病理特征和肾脏生存的危险因素。
UNASSIGNED:我们纳入了79例活检证实为LN相关TMA的患者,并与对照组相同数量的无TMA的LN患者相匹配。甘露糖结合凝集素(MBL)的沉积,MBL相关丝氨酸蛋白酶1/3(MASP1/3),补体因子B(CFB),补体因子D(CFD),C4d,通过免疫组织化学和免疫荧光法评估肾组织中的血管性血友病因子(VWF)。此外,共聚焦显微镜检测C5b-9和CD34的共定位。
未经评估:在我们的回顾性队列中,急性肾损伤的发生率(30%vs.14%,p=0.013),急性血液透析(35%vs.5%,p<0.001),和间质纤维化(43%vs.13%,p<0.001)在TMA中更高,与对照组相比。尽管有积极的类固醇脉冲,血浆置换,TMA组的免疫抑制治疗,他们的3年肾脏生存率仍然明显较差(68%vs.89%,p=0.002)比非TMA组。COX回归分析确定TMA(HR4.807,95%CI[2.052,11.263],p<0.001)是LN的危险因素。MBL,MASP1/3,CFB,CFD,C4d,VWF沿着LN中的肾小球沉积,而TMA具有更强的染色强度和沉积。在肾组织中也观察到CD34和C5b-9在内皮细胞中的共定位表达。
未经证实:TMA是LN患者肾脏存活的独立危险因素。此外,LP和AP激活参与LN相关TMA的发病机制。
The pathogenesis of thrombotic microangiopathy (TMA) in lupus nephritis (LN) remains complicated. This study aimed to detect the deposition of complement lectin pathway (LP) and alternative pathway (AP) components in renal tissues, then evaluate the clinicopathological characteristics and risk factors for renal survival between patients with or without TMA in LN cohorts.
We included 79 patients with biopsy-proven LN-associated TMA and matched the same number of LN patients without TMA as the control group. The deposition of mannose binding lectin (MBL), MBL-associated serine proteases 1/3 (MASP1/3), complement factor B (CFB), complement factor D (CFD), C4d, and von Willebrand factor (VWF) in renal tissue was assessed by immunohistochemistry and immunofluorescence. Besides, co-localization of C5b-9 and CD34 was detected by confocal microscopy.
In our retrospective cohort, the incidence of acute kidney injury (30% vs. 14%, p = 0.013), acute hemodialysis (35% vs. 5%, p < 0.001), and interstitial fibrosis (43% vs. 13%, p < 0.001) is higher in the TMA, compared with the control group. Despite aggressive steroids pulse, plasma exchange, and immunosuppressive therapy among TMA group, they still had significantly inferior 3-year renal survival rates (68% vs. 89%, p = 0.002) than those in the non-TMA group. COX regression analysis identified that TMA (HR 4.807, 95% CI [2.052, 11.263], p < 0.001) is a risk factor in LN. MBL, MASP1/3, CFB, CFD, C4d, and VWF deposited along the glomerulus among LN, while TMA had stronger staining intensity and deposition. The co-localized expression of CD34 and C5b-9 in the endothelial cells was also observed in the renal tissues.
TMA is an independent risk factor for renal survival in LN patients. Moreover, LP and AP activation are involved in the pathogenesis of LN-associated TMA.