Ministry of Education (MOE) Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, China.
Renal Division, Peking University First Hospital, Beijing, China.
Front Immunol. 2023 Apr 17;14:1181561. doi: 10.3389/fimmu.2023.1181561. eCollection 2023.
The aim of this study is to explore the prevalence and clinicopathological associations between anti-C1qA08 antibodies and anti-monomeric CRP (mCRP) a.a.35-47 antibodies and to explore the interaction between C1q and mCRP.
Ninety patients with biopsy-proven lupus nephritis were included from a Chinese cohort. Plasma samples collected on the day of renal biopsy were tested for anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies. The associations between these two autoantibodies and clinicopathologic features and long-term prognosis were analyzed. The interaction between C1q and mCRP was further investigated by ELISA, and the key linear epitopes of the combination of cholesterol binding sequence (CBS; a.a.35-47) and C1qA08 were tested by competitive inhibition assays. The surface plasmon resonance (SPR) was used to further verify the results.
The prevalence of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were 50/90 (61.1%) and 45/90 (50.0%), respectively. Levels of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were negatively correlated with serum C3 concentrations ((0.5(0.22-1.19) g/L vs. 0.39(0.15-1.38) g/L, =0.002) and (0.48(0.44-0.88) g/L vs. 0.41(0.15-1.38) g/L, =0.028), respectively. Levels of anti-C1qA08 antibodies were correlated with the score of fibrous crescents and tubular atrophy (r=-0.256, =0.014 and r=-0.25, =0.016, respectively). The patients with double positive antibodies showed worse renal prognosis than that of the double negative group (HR 0.899 (95% CI: 0.739-1.059), =0.0336). The binding of mCRP to C1q was confirmed by ELISA. The key linear epitopes of the combination were a.a.35-47 and C1qA08, which were confirmed by competitive inhibition experiments and SPR.
The combination of anti-C1qA08 and anti-mCRP a.a.35-47 autoantibodies could predict a poor renal outcome. The key linear epitopes of the combination of C1q and mCRP were C1qA08 and a.a.35-47. A08 was an important epitope for the classical pathway complement activation and a.a.35-47 could inhibit this process.
本研究旨在探讨抗 C1qA08 抗体和抗单体 CRP(a.a.35-47)抗体在狼疮肾炎患者中的流行率及与临床病理的关系，并探讨 C1q 与 mCRP 之间的相互作用。
从中国队列中纳入 90 例经肾活检证实的狼疮肾炎患者。在肾活检当天采集血浆样本，检测抗 C1qA08 抗体和抗 mCRP a.a.35-47 抗体。分析这些自身抗体与临床病理特征和长期预后的关系。采用 ELISA 进一步研究 C1q 与 mCRP 的相互作用，并通过竞争抑制实验检测胆固醇结合序列（CBS；a.a.35-47）与 C1qA08 结合的关键线性表位。表面等离子体共振（SPR）进一步验证了实验结果。
抗 C1qA08 抗体和抗 mCRP a.a.35-47 抗体的阳性率分别为 50/90（61.1%）和 45/90（50.0%）。抗 C1qA08 抗体和抗 mCRP a.a.35-47 抗体的水平与血清 C3 浓度呈负相关（(0.5(0.22-1.19) g/L vs. 0.39(0.15-1.38) g/L，=0.002）和（0.48(0.44-0.88) g/L vs. 0.41(0.15-1.38) g/L，=0.028）。抗 C1qA08 抗体的水平与纤维性新月体和肾小管萎缩的评分相关（r=-0.256，=0.014 和 r=-0.25，=0.016）。双阳性抗体组的患者肾脏预后较双阴性组差（HR 0.899（95%CI：0.739-1.059），=0.0336）。ELISA 证实 mCRP 与 C1q 的结合。竞争抑制实验和 SPR 进一步证实，该复合物的关键线性表位是 a.a.35-47 和 C1qA08。
抗 C1qA08 与抗 mCRP a.a.35-47 自身抗体的联合可预测不良肾脏结局。C1q 与 mCRP 结合的关键线性表位是 C1qA08 和 a.a.35-47。A08 是经典途径补体激活的重要表位，a.a.35-47 可抑制这一过程。
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