探讨免疫检查点和免疫细胞在诊断和治疗强直性脊柱炎中的联合作用:一项初步研究 强直性脊柱炎中的免疫检查点

IF 4.9 2区 医学 Q1 Medicine Arthritis Research & Therapy Pub Date : 2024-06-04 DOI:10.1186/s13075-024-03341-6
Feihong Huang, Zhiping Su, Yibin Huang, Yuxiang Huang, Chengyu Zhou, Sitan Feng, Xiong Qin, Xi Xie, Chong Liu, Chaojie Yu
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引用次数: 0

摘要

免疫检查点已成为治疗自身免疫性疾病的有望靶点。然而,免疫检查点在强直性脊柱炎(AS)病理生理学中的具体作用仍不清楚。研究人员从两组接受髋关节置换术的患者中采集了髋关节韧带样本:一组是患有强直性脊柱炎和股骨头畸形的患者,另一组是患有股骨头坏死但没有强直性脊柱炎的患者。采用无标记定量(LFQ)蛋白质公园分析法确定韧带的蛋白质组成。公共数据库中 104 例 AS 患者的外周血样本被用来验证关键蛋白的表达。利用KEGG、GO和GSVA探索免疫检查点在强直性脊柱炎进展中调控的潜在通路。利用xCell计算细胞浸润水平,应用LASSO回归选择关键细胞,并分析免疫检查点与免疫细胞之间的相关性。进行了药物敏感性分析,以确定针对强直性脊柱炎免疫检查点的潜在治疗药物。通过免疫组织化学(IHC)验证了关键基因的表达。HLA-DMB和HLA-DPA1在强直性脊柱炎韧带中下调,这一点已通过外周血数据集和IHC得到验证。在强直性脊柱炎患者的 CD8 + Tcm、CD8 + T 细胞、CD8 + Tem、成骨细胞、Th1 细胞和 CD8 + 天真 T 细胞中观察到明显的表达差异。CD8 + Tcm和CD8 +幼稚T细胞的浸润水平与HLA-DMB和HLA-DPA1的表达水平呈显著正相关。使用 LASSO 回归法进行的免疫细胞选择对强直性脊柱炎显示出良好的预测能力,三个预测模型的 AUC 值分别为 0.98、0.81 和 0.75。此外,该研究还发现,HLA-DMB和HLA-DPA1参与了Th17细胞的分化,而在AS组中,Th17细胞分化和NF-kappa B信号通路均被激活。药物敏感性分析表明,强直性脊柱炎患者对多拉帕莫德和GSK269962A等药物更敏感。免疫检查点和免疫细胞可作为探索强直性脊柱炎诊断和治疗策略的途径。
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Exploration of the combined role of immune checkpoints and immune cells in the diagnosis and treatment of ankylosing spondylitis: a preliminary study immune checkpoints in ankylosing spondylitis
Immune checkpoints have emerged as promising therapeutic targets for autoimmune diseases. However, the specific roles of immune checkpoints in the pathophysiology of ankylosing spondylitis (AS) remain unclear. Hip ligament samples were obtained from two patient groups: those with AS and femoral head deformity, and those with femoral head necrosis but without AS, undergoing hip arthroplasty. Label-Free Quantification (LFQ) Protein Park Analysis was used to identify the protein composition of the ligaments. Peripheral blood samples of 104 AS patients from public database were used to validate the expression of key proteins. KEGG, GO, and GSVA were employed to explore potential pathways regulated by immune checkpoints in AS progression. xCell was used to calculate cell infiltration levels, LASSO regression was applied to select key cells, and the correlation between immune checkpoints and immune cells was analyzed. Drug sensitivity analysis was conducted to identify potential therapeutic drugs targeting immune checkpoints in AS. The expression of key genes was validated through immunohistochemistry (IHC). HLA-DMB and HLA-DPA1 were downregulated in the ligaments of AS and this has been validated through peripheral blood datasets and IHC. Significant differences in expression were observed in CD8 + Tcm, CD8 + T cells, CD8 + Tem, osteoblasts, Th1 cells, and CD8 + naive T cells in AS. The infiltration levels of CD8 + Tcm and CD8 + naive T cells were significantly positively correlated with the expression levels of HLA-DMB and HLA-DPA1. Immune cell selection using LASSO regression showed good predictive ability for AS, with AUC values of 0.98, 0.81, and 0.75 for the three prediction models, respectively. Furthermore, this study found that HLA-DMB and HLA-DPA1 are involved in Th17 cell differentiation, and both Th17 cell differentiation and the NF-kappa B signaling pathway are activated in the AS group. Drug sensitivity analysis showed that AS patients are more sensitive to drugs such as doramapimod and GSK269962A. Immune checkpoints and immune cells could serve as avenues for exploring diagnostic and therapeutic strategies for AS.
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来源期刊
CiteScore
8.60
自引率
2.00%
发文量
261
审稿时长
14 weeks
期刊介绍: Established in 1999, Arthritis Research and Therapy is an international, open access, peer-reviewed journal, publishing original articles in the area of musculoskeletal research and therapy as well as, reviews, commentaries and reports. A major focus of the journal is on the immunologic processes leading to inflammation, damage and repair as they relate to autoimmune rheumatic and musculoskeletal conditions, and which inform the translation of this knowledge into advances in clinical care. Original basic, translational and clinical research is considered for publication along with results of early and late phase therapeutic trials, especially as they pertain to the underpinning science that informs clinical observations in interventional studies.
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