探索UVB敏感性与SLE活动的相关性：对UVB驱动的红斑狼疮发病机制的见解

IF 7.9 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity Pub Date : 2025-03-26 DOI:10.1016/j.jaut.2025.103393

Jiayu He , Yuanning Guo , Jiamin Chen , Jinhua Xu , Xiaohua Zhu

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引用次数: 0

摘要

红斑狼疮（Lupus erythematosus， LE）包括多种自身免疫性炎症性疾病，皮肤性红斑狼疮（CLE）和系统性红斑狼疮（SLE）之间有明显的重叠。CLE和SLE的一个关键特征是紫外线光敏性，特别是与紫外线暴露相关的皮肤炎症。尽管如此，与LE活性密切相关的可靠和客观的UVB光敏指标尚未确定，并且将UVB敏感性与LE发生和进展联系起来的潜在细胞和分子机制仍不清楚。我们发现紫外线B最小红斑剂量（UVB-MED），一种定量光敏测量，是SLE活动的一个重要和独立的危险因素，与SLEDAI呈负相关(r = - 0.58, P <；0.0001)。对大规模CLE和SLE样本（发现5918例，验证数据集7242例）的综合转录组学分析显示，与血液相比，皮肤组织中uvb反应基因失调更为明显和广泛。此外，我们还发现了14个与狼疮活动相关的uhbv应答基因（UVBACGs），包括8个I型干扰素刺激基因（IRF7、ISG20、ISG15、IFI44、IFITM1、MX1、LY6E、OASL）和其他基因（JUN、PTTG1、HLA-F、CAV1、HOPX、RPL3），在皮肤、血液和受影响器官（如肾脏和滑膜）中存在明显的失调。免疫细胞是这种失调的主要载体。常规LE治疗和I型干扰素靶向治疗被发现与这些基因相关，并可能调节它们，从而有助于治疗效果。这些发现强调了UVB在触发皮肤自身免疫性炎症中的作用，这种炎症可能随后通过免疫细胞和因子扩散到全身炎症。UVBACGs在这一过程中发挥着关键作用，可能作为精确治疗的靶点，为了解UVB光敏性与LE发病机制之间的联系提供了线索。

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Exploring the correlation between UVB sensitivity and SLE activity: Insights into UVB-driven pathogenesis in lupus erythematosus

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Exploring the correlation between UVB sensitivity and SLE activity: Insights into UVB-driven pathogenesis in lupus erythematosus

Lupus erythematosus (LE) comprises various autoimmune inflammatory diseases, with significant overlap between cutaneous LE (CLE) and systemic LE (SLE). A key feature of both CLE and SLE is UV photosensitivity, particularly in UV-exposure-related skin inflammation. Despite this, reliable and objective UVB photosensitivity indicators closely correlating with LE activity have yet to be identified, and the underlying cellular and molecular mechanisms linking UVB sensitivity with LE onset and progression remain unclear.

We discovered that ultraviolet B minimal erythema dose (UVB-MED), a quantitative photosensitivity measure, is a significant and independent risk factor for SLE activity, demonstrating a negative correlation with SLEDAI (r = −0.58, P < 0.0001). Comprehensive transcriptomic analyses of large-scale CLE and SLE samples (5918 in discovery and 7242 in validation datasets) revealed more pronounced and extensive UVB-response gene dysregulation in skin tissues compared to blood. Additionally, 14 lupus activity-correlated, UVB-response genes (UVBACGs) were identified, including eight type I interferon-stimulated genes (IRF7, ISG20, ISG15, IFI44, IFITM1, MX1, LY6E, OASL) and others (JUN, PTTG1, HLA-F, CAV1, HOPX, RPL3), with dysregulation evident in skin, blood, and affected organs (e.g., kidney and synovium). Immunocytes serve as the primary carriers of this dysregulation. Conventional LE therapies and type I interferon-targeted therapies were found to be associated with these genes and can potentially regulate them, thereby contributing to therapeutic effects.

These findings highlight the role of UVB in triggering autoimmune inflammation in the skin, which may subsequently spread to systemic inflammation via immune cells and factors. UVBACGs play a critical role in this process and may serve as targets for precise therapies, providing insight into the link between UVB photosensitivity and LE pathogenesis.

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来源期刊

Journal of autoimmunity 医学-免疫学

CiteScore

27.90

自引率

1.60%

发文量

117

审稿时长

17 days

期刊介绍： The Journal of Autoimmunity serves as the primary publication for research on various facets of autoimmunity. These include topics such as the mechanism of self-recognition, regulation of autoimmune responses, experimental autoimmune diseases, diagnostic tests for autoantibodies, as well as the epidemiology, pathophysiology, and treatment of autoimmune diseases. While the journal covers a wide range of subjects, it emphasizes papers exploring the genetic, molecular biology, and cellular aspects of the field. The Journal of Translational Autoimmunity, on the other hand, is a subsidiary journal of the Journal of Autoimmunity. It focuses specifically on translating scientific discoveries in autoimmunity into clinical applications and practical solutions. By highlighting research that bridges the gap between basic science and clinical practice, the Journal of Translational Autoimmunity aims to advance the understanding and treatment of autoimmune diseases.