Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) as a Severity and Response Biomarker in Psoriatic Arthritis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Analysis of T cell subset and dendritic cell (DC) subset for DC-STAMP expression
研究概览
简要总结
The purpose of this study is to determine whether DC-STAMP, a protein on the surface of osteoclast precursors (OCPs), can be used as a biologic marker in Psoriatic Arthritis (PsA). With this marker the investigators hope to learn more about how OCPs develop as well as find out if DC-STAMP predicts PsA severity and how well treatment works in PsA.
详细描述
Psoriatic Arthritis (PsA), a phenotypically heterogeneous disorder, is characterized by joint damage observed in over half of the patients with early disease. While anti-tumor necrosis factor (TNF) agents have greatly improved signs and symptoms and lessened joint damage, the fact that only a fraction of patients achieve complete remission underscores the tremendous unmet need for this population. To date, a biomarker that can stratify patients by severity and can serve as a leading indicator of treatment response has not been identified.
Our laboratory demonstrated that circulating osteoclast precursors (OCP) are elevated in PsA patients. OCP decline rapidly following anti-TNF therapy and levels are higher in subjects with erosive arthritis compared to those with no x-ray changes. The OCP are derived from CD14+ monocytes and the assay entails culture techniques that are costly, expensive and labor intensive. We developed an antibody (1A2) to Dendritic Cell Specific Transmembrane Protein (DC-STAMP), a potential marker of the OCP population, for analysis by flow cytometry. We found that: 1) the level of monocyte DC-STAMP expression correlated with in vitro osteoclast formation; 2) DC-STAMP expression is significantly elevated in PBMC from PsA subjects compared to controls; 3) TNF dramatically upregulated the expression of DC-STAMP in vitro; 4) DC-STAMP surface expression declined following anti-TNF therapy; 5) subsets of CD3+ cells also express DC-STAMP on the cell membrane. Based on these preliminary data, three hypotheses are proposed:
- DC-STAMP+ CD3+ T cells belong to the Th17 subset which facilitates OC generation;
- DC-STAMP is a marker of disease severity in PsA;
- DC-STAMP is a biomarker of treatment response in PsA.
We propose three Specific Aims to test these hypotheses.
Aim 1 To examine whether DC-STAMP+CD3+ cells belong to the Th17 cell subset, PBMC will be stained with Th17-specific antibodies in PsA subjects with elevated DC-STAMP expression. We will also examine the role of T cells in osteoclastogenesis directly by co-culture experiments and we will use monocyte cultures without added lymphocytes as controls. The expression of DC-STAMP on circulating dendritic cells will be examined ex vivo with 11-color flow cytometry.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must be >18 years old
- •Subject must have >3 tender and swollen joints
- •Subject must have must have a target lesion of greater than 3 cm in diameter
- •Subjects who meet the the ClASsification of Psoriatic ARthritis (CASPAR) criteria for PsA
- •Subjects must have a DC-STAMP pattern III or IV
排除标准
- •Subjects with active inflammatory synovitis, dactylitis, enthesitis, osteoarthritis, axial disease, Subjects with a SLE, Sjogren's syndrome, scleroderma or inflammatory muscle disease
- •Subjects with an active malignancy
- •Subjects currently on biologic agents (anti-TNF agents, anti-T or B cells agents) and/or disease-modifying antirheumatic drugs (DMARDs) (methotrexate, leflunomide, hydroxychloroquine, azulfidine, cyclosporine, azathioprine)
- •Subjects who have been off DMARDs or biologics for less than 3 months
- •Subjects judged ineligible at the discretion of the PI
- •Subjects with a history of crystalline arthritis (gout, pseudogout)
- •Subject pregnancy or breast feeding
- •History of recurrent infections - AIM 3 Specific
- •Demyelinating disorders - AIM 3 Specific
- •Prior non-responsiveness to TNFi - AIM 3 Specific
- •Subjects who have a BMI >30 - AIM 3 Specific MTX arm
- •Subjects who have a history of type II diabetes - AIM 3 Specific MTX arm
- •Subjects with a history of substance abuse including alcohol - AIM 3 Specific MTX arm
研究组 & 干预措施
Anti-TNF
干预措施: Anti-TNF (Drug)
Methotrexate
干预措施: Methotrexate (Drug)
结局指标
主要结局
Analysis of T cell subset and dendritic cell (DC) subset for DC-STAMP expression
时间窗: Week 0 (Baseline)
Determine whether DC-STAMP+ cells belong to the Th17 subset and also analyze the DC subsets for DC-STAMP expression.
DC-STAMP as a biomarker of treatment response in PsA
时间窗: Week 16
A measurement of DC-STAMP as a response marker to treatment will be collected. Ten subjects received methotrexate and ten received anti-TNF therapy. The correlation between DC-STAMP variables (percentage of 1A2+ divided by 1A2 - cells X 100) and the variables detailed in Aim 2 will be analyzed in these 2 treatment groups at 2 different time points.
Analysis of T cell subset and DC subset for DC-STAMP expression
时间窗: Week 16
Determine whether DC-STAMP+ cells belong to the Th17 subset and also analyze the DC subsets for DC-STAMP expression.
DC-STAMP as a marker of disease severity in PsA
时间窗: Week 16
Measurement of DC-STAMP expression will be collected in order to assist in determining whether it is associated with more severe features of PsA. DC-STAMP expression will be correlated with clinical variables of arthritis and skin disease, CRP and x-ray damage.
次要结局
未报告次要终点
研究者
Christopher Ritchlin
M.D., M.P.H.; Professor of Medicine Allergy, Immunology & Rheumatology Division
University of Rochester