Lupus Omics Cutaneous Kidney Investigative Team (LOCKIT) - Pain Supplement

狼疮组学皮肤肾脏调查小组 (LOCKIT) - 疼痛补充剂

• 批准号: 10861419
• 负责人: Jill P Buyon
• 金额: $ 35.66万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-21 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10861419
• 关键词: Acceleration; Address; Administrative Supplement; Affect; Anxiety; Autoimmune; Autoimmune Diseases; Baseline Surveys; Biological Markers; Biopsy; Brain imaging; Cells; Characteristics; Clinical; Collaborations; Collection; Consultations; Cutaneous; Data; Databases; Disease; Disease Pathway; Dissociation; Enrollment; Fatigue; Fibromyalgia; Functional disorder; Future; Goals; Immune; Immunohistochemistry; Individual; Inflammation; Institution; Investments; Ion Channel; Kidney; Knowledge; Laboratories; Lead; Leadership; Life; Lupus; Lupus Nephritis; Measures; Mediating; Medicine; Mental Depression; Methods; Mission; Modality; Molecular; Molecular Disease; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; Nephritis; Nerve; Nerve Fibers; Neuronal Plasticity; Neuropathy; Neuropeptides; Nociception; Organ; Outcome; Outcome Assessment; Pain; Pain Measurement; Pain Research; Pain interference; Pathogenesis; Patients; Phenotype; Physical Function; Physicians; Prevalence; Pruritus; Psoriasis; Psoriatic Arthritis; Quality of life; Race; Research; Rheumatism; Rheumatoid Arthritis; Severities; Site; Sjogren' s Syndrome; Skin; Sleep disturbances; Social isolation; Stains; Stromal Cells; Subgroup; Surveys; Symptoms; Syndrome; Synovial Membrane; Systemic Lupus Erythematosus; Testing; Therapeutic; Time; Tissues; Visualization; base; brain magnetic resonance imaging; burden of illness; central sensitization; chronic pain; clinical pain; comparative; density; expectation; experience; high dimensionality; indexing; innovation; insight; keratinocyte; lupus cutaneous; meetings; member; microbiome; multi-ethnic; novel; pain catastrophizing; pain symptom; painful neuropathy; parent grant; participant enrollment; patient subsets; programs; recruit; response; skin disorder; tissue injury; transcriptome sequencing; transcriptomic profiling; transcriptomics; treatment response

Clinical pain phenotypes and mechanisms in rheumatic diseases are poorly understood. The Accelerating Medicines Partnership Autoimmune and Immune-Mediated Disease (AMP AIM) Program addresses common themes across autoimmune diseases, and delineating the complexity and impact of pain and the dissociation between patient and physician perceived disease burden not necessarily related to untreated inflammation is a major unmet need. Pain phenotypes such as nociceptive (tissue injury), nociplastic (central sensitization), and neuropathic pain and their contribution to therapeutic non-response constitutes a critical knowledge gap. Pain is a core domain affecting quality of life from the perspective of patients with Systemic Lupus Erythematosus (SLE), Psoriatic Spectrum Disorder (PSD), Rheumatoid Arthritis (RA) and Sjögren’s Disease (SjD). This supplement will utilize skin biopsies acquired by the SLE and PSD disease teams in those with cutaneous disease to identify novel pain biomarkers. Patients with lupus nephritis and SjD will be included given the importance of pain in these patients as well and to provide further comparative insights. Governance will be under the leadership of Jill Buyon (mPI SLE) and Alexis Ogdie (mPI PSD) with collaboration provided by other members of the respective disease teams and consultation by Yvonne Lee bringing expertise in pain phenotyping. In parallel, efforts will be harmonized in RA and PSD with a focus on synovial biopsies. Two specific aims are proposed. In Aim 1, pain phenotypes will be delineated in patients with SLE, PSD, and SjD. In addition to the PROMIS 29 measures, patients consecutively enrolled will complete the 2016 Fibromyalgia (FM) Survey Criteria and pain catastrophizing scale. Over 2 years, the SLE team will enroll patients with active skin disease (N=20) and/or new onset nephritis (N=40), the PSD team will enroll patients with psoriasis and/or PSA (N=30), and patients with varying clinical and/or laboratory characteristics consistent with SjD (N=20) will be recruited by this third team. In Aim 2, differences in skin biomarkers and functional brain MRI among patients with SLE, PSD, and SjD with and without concomitant FM or pain sensitization will be assessed. This aim leverages studies planned to investigate lesional and non-lesional skin from patients with cutaneous LE and PSD to test the hypothesis that local nerves play a role in pain sensitization and itch. Following baseline surveys, a subset of patients with skin biopsies with differing pain phenotypes will undergo functional brain imaging. With systematic collection of deeply phenotyped patients and extensive omics derived from tissue as a part of AMP AIM, substantial innovations in pain research are expected.

风湿性疾病的临床疼痛表型和机制知之甚少。加速 药物伙伴关系自身免疫和免疫介导的疾病（AMP AIM）计划解决常见的 跨自身免疫性疾病的主题，并描绘疼痛和解离的复杂性和影响， 在患者和医生之间，认为疾病负担不一定与未经治疗的炎症相关， 未满足的重大需求。疼痛表型，如伤害性（组织损伤），伤害性（中枢致敏），和 神经性疼痛及其对治疗无反应的贡献构成了关键的知识缺口。疼痛是 从系统性红斑狼疮（SLE）患者的角度来看，这是影响生活质量的核心领域， 银屑病谱系障碍（PSD）、风湿性关节炎（RA）和干燥病（SjD）。这种补充剂 将利用SLE和PSD疾病团队在皮肤病患者中获得的皮肤活检， 新的疼痛生物标志物。考虑到疼痛在治疗中的重要性，将纳入狼疮性肾炎和SjD患者。 这些患者也是如此，并提供进一步的比较见解。治理工作将由 Jill Buyon（mPI SLE）和Alexis Ogdie（mPI PSD）与各自的其他成员合作 疾病团队和咨询Yvonne Lee带来的疼痛表型的专业知识。与此同时，将努力 在RA和PSD中协调，重点是滑膜活检。提出了两个具体目标。目标1：疼痛 将在SLE、PSD和SjD患者中描述表型。除了PROMIS 29措施外， 连续入组的患者将完成2016年纤维肌痛（FM）调查标准， 灾难规模在2年内，SLE团队将招募活动性皮肤病患者（N=20）和/或新发 发病性肾炎（N=40），PSD团队将招募银屑病和/或PSA患者（N=30）以及患有 第三组将招募符合SjD的不同临床和/或实验室特征的患者（N=20）。 在目标2中，SLE、PSD和SjD患者的皮肤生物标志物和功能性脑MRI的差异， 并且没有伴随FM或疼痛致敏。这一目标利用了计划进行的研究， 研究皮肤LE和PSD患者的病变和非病变皮肤，以检验以下假设： 局部神经在疼痛敏化和瘙痒中起作用。在基线调查后，一部分皮肤病患者 具有不同疼痛表型的活组织检查将进行功能性脑成像。通过系统的收集， 作为AMP AIM的一部分，表型患者和来自组织的广泛组学， 预计将进行疼痛研究。