Molecular Markers in Discoid Lupus Erythematous

盘状红斑狼疮的分子标记

• 批准号: 9103862
• 负责人: Benjamin Franklin Chong
• 金额: $ 16.04万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9103862
• 关键词: Affect; Apoptosis; Award; Biopsy; Blood Circulation; CD8B1 gene; CXCL10 gene; CXCR3 gene; Carbon; Cell Culture Techniques; Cell Surface Proteins; Cell surface; Cells; Cellular Immunity; Cicatrix; Classification; Clinical Investigator; Clinical Sciences; Complement Factor B; Culture Media; Cutaneous; Cutaneous Lupus Erythematosus; Data; Development Plans; Diagnosis; Diagnostic Procedure; Discoid Lupus Erythematosus; Disease; Disease Progression; Etiology; FRAP1 gene; Flow Cytometry; Foundations; Funding; Gender; Gene Expression; Gene Expression Profile; Gene Proteins; Genes; Goals; Granzyme; Human; Immunologics; Immunology; Individual; Inflammatory; Inflammatory Infiltrate; Interferon Type I; Interferons; Knowledge; Lesion; Link; Lupus; Medical center; Mentors; Mentorship; Microarray Analysis; Molecular Profiling; Mus; Nuclear; PI3K/AKT; Pathogenesis; Pathology; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Physicians; Play; Polymerase Chain Reaction; Proteins; Research Project Grants; Research Proposals; Resources; Role; Site; Skin; Skin Aging; Symptoms; Systemic Lupus Erythematosus; Systemic disease; T-Lymphocyte; Tantalum; Texas; Time; Training; Translational Research; Tumor Necrosis Factor Receptor; United States National Institutes of Health; Universities; Ursidae Family; base; career; career development; cytokine; cytotoxic; differential expression; disability; disease registry; education research; insight; lupus-like; molecular marker; new therapeutic target; novel strategies; protein biomarkers; protein expression; skin lesion; transcriptome; treatment planning

DESCRIPTION (provided by applicant): The NIH K23 mentored award provides the necessary foundation for me to fulfill my career goals of being an independently-funded clinical investigator focusing on the gene and immunologic profiles of cutaneous lupus erythematosus (CLE) patients and becoming an expert in forecasting systemic involvement in CLE patients. The mentored award will also help me achieve my immediate goals of obtaining expertise in microarrays and skin immunology, and establishing a disease registry. Under the auspices of the University of Texas Southwestern (UTSW) Medical Center, I hope to attain these objectives through: 1) mentorship from a group of nationally recognized physicians who are experts in microarrays and skin immunology, and have established disease registries, and 2) classroom education and research resources afforded through the NIH Clinical and Translational Science Award at UTSW. My mentored research project centers on discoid lupus erythematosus (DLE), a disease whose etiology is not well understood. Because of its association with systemic lupus erythematosus (SLE), discoid skin lesions represent an untapped, yet easily accessible resource that could bear great relevance to SLE pathogenesis. This project seeks to identify genes distinctive to DLE (Aim 1), proteins highly expressed by DLE skin resident T cells (Aim 2), and genes linked to systemic spread in DLE subjects (Aim 3). Aim 1 compares gene expression profiles of the skin of DLE subjects without SLE (DLE-only) and normal controls to better define DLE. We will perform microarray analyses on active discoid lesional skin and age-, gender-, and site-matched normal skin. We predict that DLE- only skin will up-regulate type I interferon-regulated and cell-mediated immunity genes versus normal skin. Aim 2 centers on protein expression of skin resident T cells, which dominate the inflammatory cell infiltrate in discoid lesions. We will isolate these T cells from DLE-only and normal skin biopsies placed on top of tantalum- coated carbon matrices and perform flow cytometry analyses to compare T cell surface protein (Study 2a) and intracellular cytokine and cytotoxic protein expression (Study 2b). We postulate that compared with their normal counterparts, DLE-only skin resident T cells will have higher expression of cell surface, cytokine, and cytotoxic proteins associated with TH1 and CD8+ T cells. Aim 3 will contrast gene profiles in DLE subjects with SLE (DLE+SLE) and DLE-only subjects to identify genes associated with systemic spread in DLE. We will perform microarray analyses on active lesional skin (Study 3a) and peripheral blood mononuclear cells (Study 3b) from both groups. We hypothesize that DLE+SLE subjects will up-regulate expression of genes regulated by tumor necrosis factor receptor, nuclear factor-�B, and PI3K/AKT/mTOR pathways compared with DLE-only subjects. Identification of genes and proteins up-regulated in DLE skin and DLE skin resident T cells, respectively, will provide greater clarity to disease pathogenesis. Moreover, knowledge of genes associated with systemic involvement in DLE subjects will enhance understanding of disease course.

描述(由申请者提供)：NIH K23导师奖为我实现自己的职业目标奠定了必要的基础，我的职业目标是成为一名独立资助的临床研究员，专注于皮肤红斑狼疮(CLE)患者的基因和免疫学特征，并成为预测CLE患者系统性病变的专家。导师奖还将帮助我实现眼前的目标，即获得微阵列和皮肤免疫学方面的专业知识，并建立一个疾病登记系统。在德克萨斯大学西南医学中心的赞助下，我希望通过以下方式实现这些目标：1)由一群全国公认的微阵列和皮肤免疫学专家提供指导，并建立疾病登记；2)通过德克萨斯大学国立卫生研究院临床和翻译科学奖提供课堂教育和研究资源。我指导的研究项目集中在盘状红斑狼疮(DLE)上，这是一种病因尚不清楚的疾病。由于与系统性红斑狼疮(SLE)有关，盘状皮肤病变是一种未开发的、但容易获得的资源，与SLE的发病机制密切相关。该项目旨在识别DLE特有的基因(目标1)、DLE皮肤驻留T细胞高表达的蛋白质(目标2)以及与DLE受试者全身传播有关的基因(目标3)。目的1比较非系统性红斑狼疮(DLE)患者(单纯DLE)和正常对照皮肤的基因表达谱，以更好地确定DLE。我们将对活跃的盘状皮损皮肤和年龄、性别和部位匹配的正常皮肤进行微阵列分析。我们预测，与正常皮肤相比，仅有DLE的皮肤将上调I型干扰素调节和细胞介导的免疫基因。目的2主要研究盘状皮损中主导炎性细胞浸润的皮肤常驻T细胞的蛋白表达。我们将从放置在涂有钽的碳基质上的仅DLE和正常皮肤活检组织中分离这些T细胞，并进行流式细胞仪分析以比较T细胞表面蛋白(研究2a)和细胞内细胞因子和细胞毒蛋白的表达(研究2b)。我们推测，与正常对照相比，仅有DLE的皮肤驻留T细胞具有更高的细胞表面、细胞因子和与TH1和CD8+T细胞相关的细胞毒蛋白的表达。目的3将比较DLE患者、SLE(DLE+SLE)患者和仅DLE患者的基因图谱，以确定与DLE全身扩散相关的基因。我们将对两组的活动性皮损(研究3a)和外周血单核细胞(研究3b)进行微阵列分析。我们假设，与仅有DLE的受试者相比，DLE+SLE受试者将上调受肿瘤坏死因子受体、核因子-�B和PI3K/AKT/mTOR通路调控的基因的表达。识别DLE皮肤和DLE皮肤驻留T细胞中上调的基因和蛋白质将为疾病发病机制提供更清晰的信息。此外，了解与DLE受试者全身参与相关的基因将增强对疾病过程的理解。

项目成果

Differences in quality of life in patients with cutaneous lupus erythematosus with varying income levels.

• DOI: 10.1177/0961203321999724
• 发表时间: 2021-05
• 期刊: Lupus
• 影响因子: 2.6
• 作者: Joseph A;Prasad S;Hynan LS;Chren MM;Chong B
• 通讯作者: Chong B

Classification of disease damage and activity in cutaneous lupus erythematosus: A cross-sectional analysis.

皮肤红斑狼疮疾病损害和活动的分类：横断面分析。

• DOI: 10.1016/j.jaad.2022.04.045
• 发表时间: 2023
• 期刊: Journal of the American Academy of Dermatology
• 影响因子: 13.8
• 作者: Abbas,LailaF;Nandy,Karabi;Chong,BenjaminF
• 通讯作者: Chong,BenjaminF

Decreased progression to systemic lupus erythematosus in patients with cutaneous lupus erythematosus under European League Against Rheumatism/American College of Rheumatology criteria.

根据欧洲抗风湿病联盟/美国风湿病学会标准，皮肤红斑狼疮患者进展为系统性红斑狼疮的速度减少。

• DOI: 10.1016/j.jaad.2022.03.048
• 发表时间: 2023
• 期刊: Journal of the American Academy of Dermatology
• 影响因子: 13.8
• 作者: Walker,AmandaM;Black,SamanthaM;Walocko,Frances;Li,Xilong;Chong,BenjaminF
• 通讯作者: Chong,BenjaminF

Older black race is a risk factor for metabolic syndrome in cutaneous lupus erythematosus.

老年黑人是皮肤红斑狼疮代谢综合征的危险因素。

• DOI: 10.1177/09612033231154785
• 发表时间: 2023
• 期刊: Lupus
• 影响因子: 2.6
• 作者: Chen,HenryW;Coias,JenniferL;Raman,Justin;Adams-Huet,Beverley;Neeland,IanJ;Chong,BenjaminF
• 通讯作者: Chong,BenjaminF

Detection of Type VII Collagen Autoantibodies Before the Onset of Bullous Systemic Lupus Erythematosus.

• DOI: 10.1001/jamadermatol.2014.4409
• 发表时间: 2015-05
• 期刊: JAMA dermatology
• 影响因子: 10.9
• 作者: Grabell DA;Matthews LA;Yancey KB;Chong BF
• 通讯作者: Chong BF