Amudzi Alice A, Piedra-Mora Cesar, Ma Diana Junyue, Wong Neil B, David Clement N, Robinson Nicholas A, Almela Ramón M, Richmond Jillian M
Dermatology Department, University of Massachusetts Chan Medical School, Worcester, MA, United States.
Pathology Department, Tufts Cummings School of Veterinary Medicine, North Grafton, MA, United States.
Front Vet Sci. 2022 Feb 24;9:778934. doi: 10.3389/fvets.2022.778934. eCollection 2022.
Cutaneous Lupus Erythematosus (CLE) is an autoimmune skin disease that occurs in almost two-thirds of people with Systemic Lupus Erythematosus (SLE) and can exist as its own entity. Despite its negative impact on the quality of life of patients, lupus pathogenesis is not fully understood. In recent years, the role of gene expression analysis has become important in understanding cellular functions and disease causation within and across species. Interestingly, dogs also develop CLE, providing a spontaneous animal model of disease. Here, we present a targeted transcriptomic analysis of skin biopsies from a case series of four dogs with complex autoimmunity with suspected CLE. We identified 92 differentially expressed genes (DEGs), including type 1 interferon, B cell, and T cell-related genes, in the four cases compared to healthy skin margin controls. Additionally, we compared our results with existing CLE datasets from humans and mice and found that humans and canines share 49 DEGs, whereas humans and mice shared only 25 DEGs in our gene set. Immunohistochemistry of IFNG and CXCL10, two of the most highly upregulated inflammatory mediators, confirmed protein-level expression and revealed immune cells as the primary source of CXCL10 in dogs with SLE, whereas keratinocytes stained strongly for CXCL10 in dogs without SLE. We propose that gene expression analysis may aid the diagnosis of complex autoimmune skin diseases and that dogs may provide important insights into CLE and SLE pathogeneses, or more broadly, skin manifestations during systemic autoimmunity.
皮肤红斑狼疮（CLE）是一种自身免疫性皮肤病，几乎三分之二的系统性红斑狼疮（SLE）患者都会出现这种疾病，并且它也可以独立存在。尽管其对患者生活质量有负面影响，但狼疮的发病机制尚未完全明确。近年来，基因表达分析在理解物种内部和跨物种的细胞功能及疾病病因方面发挥了重要作用。有趣的是，狗也会患上CLE，这为该疾病提供了一个自发的动物模型。在此，我们对一系列4只疑似患有复杂自身免疫性CLE的犬只的皮肤活检样本进行了靶向转录组分析。与健康皮肤边缘对照相比，我们在这4个病例中鉴定出92个差异表达基因（DEG），包括1型干扰素、B细胞和T细胞相关基因。此外，我们将我们的结果与来自人类和小鼠的现有CLE数据集进行了比较，发现人类和犬类共有49个DEG，而在我们的基因集中，人类和小鼠仅共有25个DEG。对两种上调程度最高的炎症介质IFNG和CXCL进行免疫组织化学分析，证实了蛋白质水平的表达，并揭示在患有SLE的犬中，免疫细胞是CXCL的主要来源，而在没有SLE的犬中，角质形成细胞对CXCL染色强烈。我们提出基因表达分析可能有助于复杂自身免疫性皮肤病的诊断，并且狗可能为CLE和SLE的发病机制，或者更广泛地说，为系统性自身免疫期间的皮肤表现提供重要见解。
