类风湿性关节炎的解构定义了炎症亚型
Fan Zhang1,2,3,4,5,6, Anna Helena Jonsson1,7, Aparna Nathan1,2,3,4,5
1Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Nature
|November 8, 2023
概括
研究人员创建了一份详细的类风湿性关节炎细胞图谱,根据细胞组成识别出不同的患者子组 (CTAP). 这种分层揭示了疾病的异质性,并预测了治疗反应,为向治疗铺平了道路.
科学领域:
- 免疫学
- 病理学
- 基因组学
背景情况:
- 风湿性关节炎是一种自身免疫性疾病,导致关节炎症和破坏.
- 目前治疗的有效性各不相同, 表明病原性多样性.
- 这种RA异质性的细胞和分子驱动因素仍然不完全理解.
研究的目的:
- 解构导致类风湿性关节炎病原异质性的细胞状态和途径.
- 创建一个完整的单细胞图谱,
- 根据细胞组成分层 RA 突组织,并评估临床效用.
主要方法:
- 多模式单细胞RNA测序和突组织表面蛋白质分析.
- 79名风湿关节炎患者的突组织组织分析.
- 细胞类型丰度表型 (CTAP) 的开发以分类突组织.
主要成果:
- 创建了一个单细胞地图,其中包含来自类风湿性关节炎突组织的314,000多个细胞.
- 鉴定出六种不同的细胞类型丰度表型 (CTAPs),反映出不同的炎症特征.
- 与特定细胞状态,细胞因子,风险基因和临床指标相关的CTAP,包括治疗反应.
结论:
- 鉴定到的CTAP突出显示了类风湿性关节炎的突发性.
- 这种基于分子和组织的分层,
- CTAP分类证明了对预测治疗反应和指导向治疗的临床实用性.
相关概念视频
T Cell Types and Functions
1.0K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.0K
The JAK-STAT Signaling Pathway
8.9K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.9K
Structural Joints: Synovial Joints
3.6K
Synovial joints are the most common type of joint in the body. A key structural characteristic for a synovial joint is the presence of a joint cavity. This fluid-filled space is where the articulating surfaces of the bones contact each other. Also, unlike fibrous or cartilaginous joints, the articulating bone surfaces at a synovial joint are not directly connected to each other with fibrous connective tissue or cartilage. This gives the bones of a synovial joint the ability to move smoothly...
3.6K
Rheumatic Heart Disease I: Introduction
14
Rheumatic heart disease or RHD is a chronic condition that results from rheumatic fever, causing permanent damage to the heart valves.Etiology and Risk FactorsIt primarily arises from rheumatic fever, an inflammatory disease that can develop after untreated or inadequately treated group A streptococcal (GAS) pharyngitis. Streptococcus spreads through direct contact with oral or respiratory secretions. While the bacteria are the causative agents, factors like malnutrition, overcrowding, poor...
14
Genome-wide Association Studies-GWAS
13.5K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
13.5K
Rheumatic Heart Disease II: Clinical Manifestations and Diagnostic Studies
37
The key clinical manifestations of Rheumatic heart disease (RHD) include several distinct cardiac symptoms.Carditis, a hallmark of acute rheumatic fever, involves inflammation of the heart's endocardium, myocardium, and pericardium. Chronic RHD often results from recurrent episodes of carditis. Its symptoms include the following:Murmurs are caused by valvular damage, especially to the mitral and aortic valves. Mitral stenosis or regurgitation is common, with characteristic heart murmurs...
37


