Discovery of new serum biomarker panels for systemic lupus erythematosus diagnosis
Discovery of new serum biomarker panels for systemic lupus erythematosus diagnosis
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发现用于系统性红斑狼疮诊断的新血清生物标志物组
DOI：
10.1093/rheumatology/kez634
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发表时间：
2020-06-01
期刊：
影响因子：
5.5
通讯作者：
Ye, Dong-Qing
中科院分区：
文献类型：
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作者：
Ling, Hua-Zhi;Xu, Shu-Zhen;Ye, Dong-Qing
objective.由于SLE的异质性，其临床诊断目前具有挑战性。许多自身抗体与SLE相关，被认为是潜在的诊断标志物，但缺乏对此类自身抗体的系统筛选和验证。本研究旨在系统地发现新的自身抗体，这些抗体可能是用于SLE诊断的良好生物标志物。使用人类蛋白质组微阵列分析了15名SLE患者和5名健康志愿者的血清，以鉴定候选SLE相关自身抗体。通过筛选来自107名SLE患者、94名健康志愿者和60名疾病对照的血清，使用由对应于所鉴定的候选抗体的自身抗原组成的聚焦阵列来验证结果。逻辑回归用于推导和验证可区分SLE疾病的自身抗体组。对294例SLE患者和461例正常人血清进行了广泛的ELISA筛选，以验证一种新发现的自身抗体。SLE组中分别有31、11和18种自身抗体的表达水平显著高于健康志愿者、疾病对照组和健康志愿者加疾病对照组，其中25、7和13种差异表达的自身抗体先前未报道。选择包含抗RPLP2、抗SNRPC和抗PARP1以及抗RPLP2、抗PARP1、抗MAK16和抗RPL7A的诊断组。通过ELISA证实了新发现的抗MAK16自身抗体的性能。SLE患者的病情活动性与抗PARP1水平有关，皮疹与抗RPLP2、抗MAK16和抗RPL7A水平有关。联合自身抗体组在SLE的诊断和其他主要风湿性免疫疾病的鉴别诊断显示出希望。
Objective. Clinical diagnosis of SLE is currently challenging due to its heterogeneity. Many autoantibodies are associated with SLE and are considered potential diagnostic markers, but systematic screening and validation of such autoantibodies is lacking. This study aimed to systematically discover new autoantibodies that may be good biomarkers for use in SLE diagnosis.Methods. Sera from 15 SLE patients and 5 healthy volunteers were analysed using human proteome microarrays to identify candidate SLE-related autoantibodies. The results were validated by screening of sera from 107 SLE patients, 94 healthy volunteers and 60 disease controls using focussed arrays comprised of autoantigens corresponding to the identified candidate antibodies. Logistic regression was used to derive and validate autoantibody panels that can discriminate SLE disease. Extensive ELISA screening of sera from 294 SLE patients and 461 controls was performed to validate one of the newly discovered autoantibodies.Results. A total of 31, 11 and 18 autoantibodies were identified to be expressed at significantly higher levels in the SLE group than in the healthy volunteers, disease controls and healthy volunteers plus disease control groups, respectively, with 25, 7 and 13 of these differentially expressed autoantibodies being previously unreported. Diagnostic panels comprising anti-RPLP2, anti-SNRPC and anti-PARP1, and anti-RPLP2, anti-PARP1, anti-MAK16 and anti- RPL7A were selected. Performance of the newly discovered anti-MAK16 autoantibody was confirmed by ELISA. Some associations were seen with clinical characteristics of SLE patients, such as disease activity with the level of anti-PARP1 and rash with the level of anti-RPLP2, anti-MAK16 and anti- RPL7A.Conclusion. The combined autoantibody panels identified here show promise for the diagnosis of SLE and for differential diagnosis of other major rheumatic immune diseases.