Utility of autoantibody against an UCH-L1 epitope as a serum diagnostic marker for neuropsychiatric systemic lupus erythematosus
Utility of autoantibody against an UCH-L1 epitope as a serum diagnostic marker for neuropsychiatric systemic lupus erythematosus
复制标题
针对 UCH-L1 表位的自身抗体作为神经精神系统性红斑狼疮血清诊断标志物的用途
DOI：
10.55563/clinexprheumatol/0bjstd
复制
发表时间：
2022-11-01
影响因子：
3.7
通讯作者：
Sun, X.
中科院分区：
文献类型：
--
作者：
Guo, Y.;Li, X.;Sun, X.
目的系统性红斑狼疮（SLE）的神经精神性病变（NPSLE）是SLE最严重的并发症之一，目前尚无有效的诊断标志物。以往的研究表明，抗泛素羧基水解酶L1（UCH-L1）自身抗体是一种很有前途的诊断NPSLE的脑脊液（CSF）生物标志物。本研究的目的是探索针对不同UCH-L1表位的血清自身抗体，并探讨针对不同UCH-L1表位的血清自身抗体在NPSLE中的潜在诊断价值。方法应用DNAStar软件预测UCH-L1蛋白的表位。采用酶联免疫吸附试验（ELISA）检测40例NPSLE患者、32例无神经精神症状的SLE患者和21例健康对照者血清中UCH-L1表位自身抗体的水平。采用Pearson相关分析、ROC曲线分析、非参数Mann-Whitney检验、t检验和χ 2检验等方法对数据进行分析。抗UCH-L1第58 - 69位氨基酸的自身抗体（UCH 58 -69）在区分NPSLE患者和无神经精神症状的SLE患者方面显示出最高的诊断能力（p=0.0038）。ROC曲线分析显示抗UCH 58 -69的特异性和敏感性分别为92.3%和37.5%。结论NPSLE患者血清抗UCH 58 - 69抗体水平明显高于无神经精神症状的SLE患者，且与疾病严重程度相关。抗UCH 58 -69自身抗体有可能成为NPSLE无创诊断的一种新的血清学标志物，可用于NPSLE的早期筛查和诊断。
Objective Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most serious complications of systemic lupus erythematosus (SLE), lacking efficient diagnostic biomarkers. Previous studies have shown that anti-ubiquitin carboxyl hydrolase L1(UCH-L1) autoantibody is a promising cerebrospinal fluid (CSF) biomarker for NPSLE diagnosis. The purpose of this study is to explore the serum autoantibodies against different UCH-L1 epitopes and investigate the potential diagnostic value of serum autoantibodies against different UCH-L1 epitopes in NPSLE. Methods The epitopes of UCH-L1 protein were predicted in DNAStar software. The serum levels of different UCH-L1 epitope autoantibodies in 40 NPSLE patients, 32 SLE patients without neuropsychiatric symptoms and 21 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). Data were analysed using Pearson correlation analysis, ROC curve analysis, nonparametric Mann-Whitney test, t-test and chi 2 test.Results We screened three candidate epitopes of UCH-L1 protein. The autoantibody against amino acid 58 to 69 of UCH-L1 (UCH58-69) showed highest diagnostic power in distinguishing NPSLE patients from SLE patients without neuro-psychiatric symptoms (p=0.0038). The ROC analysis showed that the specificity and sensitivity of anti-UCH58-69 were 92.3% and 37.5%, respectively. In addition, increased serum anti-UCH58-69 levels were associated with increased SLEDAI, CSF microprotein, CSF leukocyte count, ESR, AnuA, anti-dsDNA, IgG and IgM but with decrease of C3 in SLE patients.Conclusion The serum levels of anti-UCH58-69 significantly increased in NPSLE patients compared with SLE patients without neuropsychiatric symptoms and were correlated with disease severity. Anti-UCH58-69 autoantibody may become a novel serum biomarker for NPSLE non-invasive diagnosis, which might be applicable for NPSLE early screening and diagnosis.