Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes
Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes
复制标题
DOI：
10.3390/jcm8081244
复制
发表时间：
2019-08-01
影响因子：
3.9
通讯作者：
Kahlenberg, J. Michelle
中科院分区：
文献类型：
--
作者：
Berthier, Celine C.;Tsoi, Lam C.;Kahlenberg, J. Michelle
皮肤红斑狼疮（CLE）是系统性红斑狼疮（SLE）的常见表现，并且CLE也可以在没有全身受累的情况下发生。 CLE 可能很难治疗，并且会对生活质量产生负面影响。尽管 CLE 很重要，但我们对区分皮肤狼疮亚型的知识仍然有限。在这里，我们利用了 90 例 CLE 病变活检的大队列来比较患有和不患有相关 SLE 的盘状红斑狼疮 (DLE) 和亚急性皮肤狼疮 (SCLE) 患者，以便辨别疾病活动的驱动因素，并可能发现更好的治疗目标。总体而言，我们发现 DLE 和 SCLE 共享许多差异表达基因 (DEG)，反映 I 型干扰素 (IFN) 信号传导和 EGFR 通路的抑制。单纯 CLE 和 SLE 相关 CLE 病变之间没有发现差异。值得注意的是，DLE 独特地表达 IFN-γ 节点。 DEG 的无偏聚类分析确定了按中性粒细胞与单核细胞特征分开的两组，这些组没有根据临床表型或疾病活动对患者进行分类。这表明对 CLE 病变病理学的公正分析对于个性化医疗和针对性治疗决策可能很重要。
Cutaneous lupus erythematosus (CLE) is a common manifestation of systemic lupus erythematosus (SLE), and CLE can also develop without systemic involvement. CLE can be difficult to treat and negatively contributes to quality of life. Despite the importance of CLE, our knowledge of what differentiates cutaneous lupus subtypes is limited. Here, we utilized a large cohort of 90 CLE lesional biopsies to compare discoid lupus erythematosus (DLE) and subacute cutaneous lupus (SCLE) in patients with and without associated SLE in order to discern the drivers of disease activity and possibly uncover better treatment targets. Overall, we found that DLE and SCLE share many differentially expressed genes (DEG) reflecting type I interferon (IFN) signaling and repression of EGFR pathways. No differences between CLE only and SLE-associated CLE lesions were found. Of note, DLE uniquely expresses an IFN-gamma node. Unbiased cluster analysis of the DEGs identified two groups separated by neutrophilic vs. monocytic signatures that did not sort the patients based on clinical phenotype or disease activity. This suggests that unbiased analysis of the pathobiology of CLE lesions may be important for personalized medicine and targeted therapeutic decision making.