Rheumatology Unit, Department of Precision Medicine, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy.
Multidisciplinary Department of Medical-Surgical and Dental Specialties, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy.
Nat Rev Rheumatol. 2023 Jun;19(6):331-342. doi: 10.1038/s41584-023-00948-y. Epub 2023 Apr 11.
Systemic lupus erythematosus (SLE) is an autoimmune disease that has diverse clinical manifestations, ranging from restricted cutaneous involvement to life-threatening systemic organ involvement. The heterogeneity of pathomechanisms that lead to SLE contributes to between-patient variation in clinical phenotype and treatment response. Ongoing efforts to dissect cellular and molecular heterogeneity in SLE could facilitate the future development of stratified treatment recommendations and precision medicine, which is a considerable challenge for SLE. In particular, some genes involved in the clinical heterogeneity of SLE and some phenotype-related loci (STAT4, IRF5, PDGF genes, HAS2, ITGAM and SLC5A11) have an association with clinical features of the disease. An important part is also played by epigenetic varation (in DNA methylation, histone modifications and microRNAs) that influences gene expression and affects cell function without modifying the genome sequence. Immune profiling can help to identify an individual's specific response to a therapy and can potentially predict outcomes, using techniques such as flow cytometry, mass cytometry, transcriptomics, microarray analysis and single-cell RNA sequencing. Furthermore, the identification of novel serum and urinary biomarkers would enable the stratification of patients according to predictions of long-term outcomes and assessments of potential response to therapy.
系统性红斑狼疮(SLE)是一种自身免疫性疾病,具有多种临床表现,从局限于皮肤的受累到危及生命的全身性器官受累不等。导致 SLE 的发病机制的异质性导致了患者之间临床表型和治疗反应的差异。目前正在努力剖析 SLE 中的细胞和分子异质性,这有助于未来制定分层治疗建议和精准医学,这对 SLE 来说是一个相当大的挑战。特别是,一些与 SLE 临床异质性相关的基因和一些表型相关的基因座(STAT4、IRF5、PDGF 基因、HAS2、ITGAM 和 SLC5A11)与疾病的临床特征有关。表观遗传变异(在 DNA 甲基化、组蛋白修饰和 microRNAs 中)也起着重要作用,它影响基因表达并影响细胞功能,而不会改变基因组序列。免疫谱分析可以使用流式细胞术、质谱流式细胞术、转录组学、微阵列分析和单细胞 RNA 测序等技术,帮助识别个体对治疗的特定反应,并有可能预测结果。此外,鉴定新的血清和尿液生物标志物将能够根据对长期结局的预测和对治疗潜在反应的评估对患者进行分层。