Zhang Huan, Deng Jiayi, Liu Yang, Xia Wen, Zhuang Lulu, Zhou Houan, Liu Zhengzhao, Zhang Haitao, Hu Weixin
National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
National Clinical Research Center for Kidney Diseases, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China.
Clin Rheumatol. 2025 Jun 11. doi: 10.1007/s10067-025-07528-3.
To explore the associations of novel serum autoantibodies with disease activity and organ injuries in patients with lupus nephritis (LN).
This study included 75 patients with active LN (5 class II, 37 class IV, and 33 class V). Indirect immunofluorescence was used to measure serum anti-dsDNA; ELISA was used to measure serum anti-PLA2R and anti-C1q, and the Luminex method was used to measure 58 novel serum autoantibodies, with a median fluorescence intensity (MFI)/threshold ≥ 1.5 as the antibody positivity cutoff.
The positivity rates for 11 novel antibodies (anti-PLA2R, anti-P2RY11, anti-DEXI, anti-HARS, anti-TUBA1B, anti-KRT8, anti-TUBB, anti-NCL, anti-HSPB1, anti-AGRN, and anti-LGALS8) were highly associated with SLE activity and were inconsistent with those for anti-dsDNA and anti-C1q. Anti-TUBA1B and anti-AGRN positivity may independently influence LN with extrarenal organ involvement (OR = 6.73, 95% CI = 1.19 ~ 38.09; OR = 6.11, 95% CI = 1.32 ~ 28.25, respectively). The positivity rate for anti-PLA2R as detected by the Luminex platform was 40%, whereas the rate among those detected by ELISA was 12.7%. Twenty-one patients who achieved renal remission were retested, and the positivity rates of anti-PLA2R (42.9% vs. 9.5%, P = 0.014), anti-KRT8 (47.6% vs. 4.8%, P = 0.001), and anti-AGRN (38.1% vs. 4.8%, P = 0.008) also significantly decreased from baseline.
On the basis of Luminex technology, the present study revealed multiple novel autoantibodies related to SLE activity and organ injury, especially anti-PLA2R, anti-KRT8, and anti-AGRN, thereby providing novel serological markers for the assessment of activity in patients with LN. Anti-TUBA1B and anti-AGRN are strongly associated with extrarenal involvement. Key Points • The Luminex method is highly sensitive and high-throughput for detecting serum autoantibodies. • LN patients with anti-TUBA1B and anti-AGRN positivity are more likely to be complicated by extrarenal organ involvement. • Serum anti-PLA2R, anti-KRT8, and anti-AGRN reflect the activity of SLE and provide novel serological markers for the evaluation of LN patients negative for anti-dsDNA and anti-C1q.
探讨新型血清自身抗体与狼疮性肾炎（LN）患者疾病活动度及器官损伤的相关性。
本研究纳入75例活动性LN患者（Ⅱ型5例、Ⅳ型37例、Ⅴ型33例）。采用间接免疫荧光法检测血清抗双链DNA；采用酶联免疫吸附测定法检测血清抗磷脂酶A2受体（anti-PLA2R）和抗C1q，采用Luminex法检测58种新型血清自身抗体，以中位荧光强度（MFI）/阈值≥1.5作为抗体阳性截断值。
11种新型抗体（anti-PLA2R、抗嘌呤能P2Y受体11型（anti-P2RY11）、抗DEXI、抗组氨酰-tRNA合成酶（anti-HARS）、抗微管蛋白α1B（anti-TUBA1B）、抗角蛋白8（anti-KRT8）、抗微管蛋白β（anti-TUBB）、抗核仁素（anti-NCL）、抗热休克蛋白B1（anti-HSPB1）、抗聚集蛋白（anti-AGRN）和抗半乳糖凝集素8（anti-LGALS8））的阳性率与系统性红斑狼疮（SLE）活动度高度相关，且与抗双链DNA和抗C1q的阳性率不一致。抗-TUBA1B和抗-AGRN阳性可能独立影响合并肾外器官受累的LN（比值比（OR）分别为6.73，95%置信区间（CI）为1.19～38.09；OR = 6.11，95%CI为1.32～28.25）。Luminex平台检测的anti-PLA2R阳性率为40%，而酶联免疫吸附测定法检测的阳性率为12.7%。对21例实现肾脏缓解的患者进行复测，anti-PLA2R（42.9%对9.5%，P = 0.014）、anti-KRT8（47.6%对4.8%，P = 0.001）和anti-AGRN（38.1%对4.8%，P = 0.008）的阳性率也较基线水平显著下降。
基于Luminex技术，本研究揭示了多种与SLE活动度及器官损伤相关的新型自身抗体，尤其是anti-PLA2R、anti-KRT8和anti-AGRN，从而为评估LN患者的活动度提供了新的血清学标志物。抗-TUBA1B和抗-AGRN与肾外受累密切相关。要点•Luminex法检测血清自身抗体具有高敏感性和高通量性。•抗-TUBA1B和抗-AGRN阳性的LN患者更易合并肾外器官受累。•血清anti-PLA2R、anti-KRT8和anti-AGRN反映SLE的活动度，为抗双链DNA和抗C1q阴性的LN患者评估提供了新的血清学标志物。
