ISSN 1006-298X      CN 32-1425/R

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肾脏病与透析肾移植杂志 ›› 2023, Vol. 32 ›› Issue (2): 101-106.DOI: 10.3969/j.issn.1006-298X.2023.02.001

• •    下一篇

抗血管紧张素Ⅱ-1型受体抗体是狼疮性肾炎活动和系统损伤的新标记

夏文, 邓佳仪, 庄璐璐, 刘洋, 谌达程, 徐峰, 刘正钊, 许书添, 左科, 张丽华, 胡伟新   

  • 出版日期:2023-04-28 发布日期:2023-04-24

Anti-angiotensin Ⅱ type 1 receptor antibody: A marker of lupus activity and organ injury in patients with lupus nephritis

XIA Wen, DENG Jiayi, ZHUANG Lulu, LIU Yang, CHEN Dacheng, XU Feng, LIU Zhengzhao, XU Shutian, ZUO Ke, ZHANG Lihua, HU Weixin   

  • Online:2023-04-28 Published:2023-04-24

摘要: 目的:探究抗血管紧张素Ⅱ-1型受体抗体(AT1R-AA)与狼疮性肾炎(LN)患者临床和病理特征的相关性。
方法:98例经肾活检确认活动性LN患者,ELISA法检测血清AT1R-AA(>17 U/mL定义为阳性)。狼疮活动所致3个及以上其他系统损伤定义为多系统受累。根据AT1R-AA与抗dsDNA或抗-C1q抗体是否同时阳性分为抗体单阳性和双阳性两组。选择18例性别年龄与LN患者匹配的健康人作为正常对照,14例患者免疫抑制治疗获得缓解时重复检测AT1R-AA。
结果:98例LN患者中位SLE疾病活动度评分(SLE-DAI)13(10,16)分,近一半存在多器官系统受累,中位血清AT1R-AA水平显著高于正常对照(17.6 U/mL vs 7.93 U/mL,P<0.001),51%患者血清AT1RAA阳性,各病理类型间AT1R水平和阳性率无差异。相关性分析发现AT1R-AA水平与SLE-DAI呈正相关(r=0.490,P<0.001),与C3(r=-0.279,P=0.005)和C4(r=-0.270,P=0.007)水平呈负相关。与AT1R-AA阴性患者相比,AT1R-AA阳性患者的SLE-DAI(P<0.001)、系统受累数(P<0.001)和多系统损伤比例(P<0.001)均显著增加,血清C3水平(P=0.021)和慢性化指数(CI)(P=0.049)显著降低,肾脏损伤指标两组间无统计学差异。与抗体单阳组比较,抗体双阳组的SLE-DAI(P<0.001)、多系统受累(P=0.037)和急性肾损伤比例(P=0.016)显著增高,而血清C3(P=0.021)和C4(P=0.022)水平显著降低。治疗后获得肾脏缓解的14例患者血清AT1R.AA水平(22.9 U/mL vs 12.4 U/mL,P=0.001)和阳性率(78.6% vs 21.4%,P=0.008)均显著下降。
结论:AT1R-AA是LN患者活动的血清学新标记,其水平与SLE-DAI及系统受累相关;AT1R-AA与抗dsDNA或抗C1q抗体共阳性患者的狼疮活动性、系统受累及肾损伤程度显著增加。


关键词: 抗血管紧张素Ⅱ-1型受体抗体, 狼疮性肾炎, 狼疮活动性

Abstract: Objective:To explore the correlation between anti-angiotensin Ⅱ Type 1 receptor antibody (AT1R-AA) and clinicopathological characteristics of patients with lupus nephritis (LN).
Methodology:98 patients with active LN confirmed by renal biopsy were evaluated for lupus activity using SLE-DAI. Renal tissue activity index (AI) and chronicity index (CI) were semi-quantitatively scored. Serum AT1R-AA was detected by ELISA (>17 U/mL defined as positive). Involvement of 3 or more other systems due to lupus activity was defined as multi-system involvement. According to whether AT1R-AA and anti-dsDNA or anti-C1q antibodies were simultaneously positive, they were divided into two groups: single positive and double positive antibodies. 18 healthy individuals matched for gender and age with LN patients were selected as normal controls. AT1R-AA was retested in 14 patients who achieved remission after immunosuppressive therapy.
Results:The median SLE-DAI score of 98 LN patients was 13 (10,16), nearly half had multi-system involvement, and the median serum AT1R-AA level in LN patients was significantly higher than that in the normal control group (17.6 U/mL vs 7.93 U/mL, P<0.001). 51% of patients had positive serum AT1RAA, and there were no difference in AT1R level and positivity rate among different pathological types. Correlation analysis showed that AT1R-AA level was positively correlated with SLE-DAI (r=0.490, P<0.001) and negatively correlated with C3 (r=-0.279, P=0.005) and C4 (r=-0.270, P=0.007) levels. Compared with AT1R-AA negative patients, AT1R-AA positive patients had significantly higher SLE-DAI scores (P<0.001), number of organ systems involved (P<0.001), and proportion of multiorgan system damage (P<0.001), significantly decreased serum C3 levels (P=0.021) and CI scores (P=0.049), and no significant difference in renal injury indicators between the two groups. Compared with the single antibody positive group, the double antibody positive group had significantly higher SLE-DAI scores (P<0.001), multiorgan system involvement (P=0.037), and acute kidney injury ratio (P=0.016), while serum C3 (P=0.021) and C4 (P=0.022) levels were significantly lower. After treatment, the serum AT1R-AA level (22.9 U/mL vs 12.4 U/mL, P=0.001) and positivity rate (78.6% vs 21.4%, P=0.008) of 14 patients who achieved renal remission were significantly reduced.
Conclusion:AT1R-AA is a new serological marker for active lupus nephritis patients, which is correlated with SLE-DAI score and system involvement. Lupus activity, organ system involvement and renal injury degree are significantly increased in patients with co-positive AT1R-AA and anti-dsDNA or anti-C1q antibodies.