Nakano Masahiro, Iwasaki Yukiko, Fujio Keishi
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Inflamm Regen. 2021 Apr 9;41(1):11. doi: 10.1186/s41232-021-00161-y.
The management of systemic lupus erythematosus (SLE) remains challenging for clinicians because of the clinical heterogeneity of this disease. In attempts to identify useful biomarkers for the diagnosis of and treatment strategies for SLE, previous microarray and RNA sequencing studies have demonstrated several disease-relevant signatures in SLE. Of these, the interferon (IFN) signature is complex, involving IFNβ- and IFNγ-response genes in addition to IFNα-response genes. Some studies revealed that myeloid lineage/neutrophil and plasma cell signatures as well as the IFN signature were correlated with disease activity, lupus nephritis, and complications of pregnancy, although some of these findings remain controversial. Cell-type-specific gene expression analysis revealed the importance of an exhaustion signature in CD8 T cells for SLE outcome. Recent single-cell RNA sequencing analyses of SLE blood and tissues demonstrated molecular heterogeneity and identified several distinct subpopulations as key players in SLE pathogenesis. Further studies are required to identify novel treatment targets and determine precise patient stratification in SLE. In this review, we discuss the findings and limitations of SLE transcriptomic studies.
由于系统性红斑狼疮(SLE)具有临床异质性,其管理对临床医生来说仍然具有挑战性。为了寻找用于SLE诊断和治疗策略的有用生物标志物,先前的微阵列和RNA测序研究已经在SLE中证实了几种与疾病相关的特征。其中,干扰素(IFN)特征较为复杂,除了IFNα反应基因外,还涉及IFNβ和IFNγ反应基因。一些研究表明,髓系谱系/中性粒细胞和浆细胞特征以及IFN特征与疾病活动、狼疮性肾炎和妊娠并发症相关,尽管其中一些发现仍存在争议。细胞类型特异性基因表达分析揭示了CD8 T细胞耗竭特征对SLE预后的重要性。最近对SLE血液和组织进行的单细胞RNA测序分析显示了分子异质性,并确定了几个不同的亚群是SLE发病机制中的关键参与者。需要进一步研究以确定新的治疗靶点并确定SLE中精确的患者分层。在本综述中,我们讨论了SLE转录组学研究的结果和局限性。