Plasma Membrane Antigens as Trigger in Cancer-associated Myositis
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 50
- 试验地点
- 4
- 主要终点
- Identification of autoantibodies against surface proteins in patients with dermatomyositis (DM) with and without cancer.
研究概览
简要总结
The project is about dermatomyositis (DM), an autoimmune disease characterized by inflammation in the skeletal muscles and skin. Patients with DM have an increased risk of cancer, with a cancer incidence between 5.5% and 42%. Cancers in these patients are one of the leading causes of death. Some myositis-specific autoantibodies have been discovered and some of them are associated with cancer development. However, DM patients negative for all the known autoantibodies can also develop cancer. The Investigator hypothesized that antibodies against plasma membrane antigens and soluble immune checkpoints can be responsible for the association between cancers and autoimmunity. Therefore, the present study aimed to identify novel antigens and immunological pathways in patients with DM with cancer versus patients with DM without cancer, to identify those patients who need cancer screening. The Investigators focus on soluble immune checkpoint molecules and autoantibodies directed against plasma membrane antigens.
详细描述
Several studies have reported an association between cancers and autoimmune diseases. Mechanisms underlying this association are largely unknown, but similarity between antigens expressed by cells in tissues targeted by autoimmune reactions and cancer cells is likely one of the drivers. Moreover, chronic inflammation can favor cancer onset.
Among autoimmune diseases, dermatomyositis (DM) has the highest association with cancers. About 25% of patients with DM, over 40 years old, have cancer at the time of diagnosis or develop cancer later. Common cancers include lung, breast, colon, prostate, and ovarian cancers. DM is a systemic inflammatory disease affecting skeletal muscle, skin, and other organs (e.g., lung). Cancer risk in patients with DM is higher compared to age- and sex-matched populations, both before diagnosis and in the three years following diagnosis (standardized incidence ratio: 3.8 - 17.29).
DM is characterized by autoantibodies. Autoantibodies against transcriptional intermediary factor TIF1-gamma, nuclear matrix protein (NXP2), and SUMO1 activating enzyme (SAE1) are detected more frequently in patients with paraneoplastic DM compared to patients without cancers and healthy controls. In contrast, autoantibodies against Jo-1 are detected less frequently. However, the identification of patients with increased cancer risk remains incomplete since DM patients negative for all known autoantibodies also have an increased risk. While TIF1-gamma, NXP2, and Jo-1 are intracellular antigens, plasma membrane antigens are more likely involved in cancer-associated DM due to their accessibility to antibodies.
Immune checkpoint molecules have emerged as key regulators of the immune system, crucial for self-tolerance and immune activation. They mainly act as ligand-receptor pairs, but several undergo alternative splicing, generating soluble isoforms. The production of soluble forms of immune checkpoints in DM is scarcely known.
Autoantibodies against extracellular antigens and soluble immune checkpoints may contribute to the association between cancers and autoimmunity. Identifying circulating markers deregulated in cancer-associated DM will enable the identification of patients at risk, facilitating timely screening and interventions.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 40 years.
- •Diagnosis of DM.
- •Informed Consent
排除标准
- •Chemotherapy at the time of the peripheral venous blood draw.
- •Therapy with biologic drugs at the time of the peripheral venous blood draw.
- •Necrotizing autoimmune myopathy.
结局指标
主要结局
Identification of autoantibodies against surface proteins in patients with dermatomyositis (DM) with and without cancer.
时间窗: At enrollement
Serum samples from patients with DM with and without cancer will be tested for their ability to bind various cell lines surface antigens through immunofluorescence assays on live cells. Median fluorescence intensity will be evaluated. These analyses will determine whether there are differences in the levels of autoantibodies between the serum samples from patients with and without cancer. Potential autoantigens will be identified by immunoprecipitation of cell lysates with sera followed by mass spectrometry.
Identification of soluble immune checkpoint molecules in patients with dermatomyositis (DM) with and without cancer.
时间窗: At Enrollment
Levels of 14 soluble immune checkpoint molecules will be quantified in serum samples using the Magpix technology (ProcartaPlex Immuno-Oncology Checkpoint Panel 1). The target molecules include: BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, CD28, CD80, CD137, CD27, and CD152. Concentrations of soluble immune checkpoints will be evaluated. These analyses will determine whether there are differences in the levels of these molecules between the serum samples from patients with and without cancer.
次要结局
- Expression of autoantigens in muscle biopsy samples from DM patients and cancer samples(At Enrollment)
- Expression of autoantibodies against surface proteins in patients with dermatomyositis (DM) compared to healthy controls.(At Enrollment)
- Expression of soluble immune checkpoint molecules in patients with dermatomyositis (DM) compared to healthy controls.(At Enrollment)