Department of Dermatology, University of Rochester Medical Center, Rochester, New York, USA.
Department of Medicine, University of Rochester Medical Center, Rochester, New York, USA.
J Invest Dermatol. 2022 Nov;142(11):2885-2895.e2. doi: 10.1016/j.jid.2022.03.033. Epub 2022 May 18.
Although B cells account for a significant proportion of the lymphocytic infiltrate in discoid lupus erythematosus (DLE), their contribution to pathogenesis is unknown. In this study, we compare the immune landscape of 17 subjects with DLE with that of 21 subjects with subacute cutaneous lupus erythematosus using transcriptomic and histologic analyses of lesional skin. A few of the subjects (3 of 17 subjects with DLE, and 5 of 21 subjects with subacute cutaneous lupus erythematosus) had concomitant systemic lupus erythematosus. Using a modified Autoimmune Profiling Panel (NanoString Technologies, Seatle, WA), we show that B-cell‒specific genes, including canonical pan‒B cell markers CD19 (P = 0.0060), MS4A1 (CD20) (P = 0.0047), and CD79a (P = 0.0201), are among the most upregulated genes in DLE. Numerous other genes encoding B-cell‒associated proteins, including Igs, BAFF receptors, and FCRL family members, are similarly enriched. Relative cell type scoring reveals that among various inflammatory cell types, only B cells are more prevalent in DLE. Digital whole-image slide analysis of immunohistochemistry for B cells (CD20) and T cells (CD3) supports our gene expression findings of a disproportionately greater B-cell infiltrate in DLE lesions. Overall, this study identifies a B-cell‒predominant signature unique to DLE and highlights the importance of studying the role of cutaneous B cells in DLE pathogenesis.
虽然 B 细胞在盘状红斑狼疮（DLE）的淋巴细胞浸润中占很大比例，但它们对发病机制的贡献尚不清楚。在这项研究中，我们通过对病变皮肤的转录组学和组织学分析，比较了 17 例 DLE 患者和 21 例亚急性皮肤型红斑狼疮患者的免疫图谱。少数患者（3 例 DLE 和 5 例亚急性皮肤型红斑狼疮）同时患有系统性红斑狼疮。使用改良的自身免疫分析面板（NanoString Technologies，西雅图，WA），我们表明 B 细胞特异性基因，包括经典的泛 B 细胞标记物 CD19（P=0.0060）、MS4A1（CD20）（P=0.0047）和 CD79a（P=0.0201），是 DLE 中上调最明显的基因之一。许多其他编码 B 细胞相关蛋白的基因，包括 Igs、BAFF 受体和 FCRL 家族成员，也同样丰富。相对细胞类型评分显示，在各种炎症细胞类型中，只有 B 细胞在 DLE 中更为常见。B 细胞（CD20）和 T 细胞（CD3）的免疫组化数字全玻片分析支持我们的基因表达发现，即 DLE 病变中 B 细胞浸润不成比例地增加。总的来说，这项研究确定了 DLE 特有的以 B 细胞为主的特征，并强调了研究皮肤 B 细胞在 DLE 发病机制中的作用的重要性。
