Serum protein profiling reveals distinct patient clusters in giant cell arteritis.

IF 4.7 2区医学 Q1 RHEUMATOLOGY Rheumatology Pub Date : 2024-10-01 DOI:10.1093/rheumatology/keae072

Flavia Zingg, Fabio S Ryser, Andrea D Gloor, Christos Polysopoulos, Peter M Villiger, Britta Maurer, Lisa Christ

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Abstract

Objectives: We investigated the potential of serum proteins for distinguishing clinical and molecular subtypes in patients with GCA.

Methods: Proximity extension assays were used to analyse 1463 proteins in serum samples from patients with new-onset GCA (n = 16) and patients who have achieved remission (n = 13). Unsupervised and supervised cluster analyses were performed.

Results: Unsupervised cluster analysis identified three distinct clusters based on the protein signature. Compared with cluster 2, patients of cluster 1 had fewer PMR symptoms, increased levels of macrophage migration inhibitory factor (MIF) and pronounced NF-κB, STAT5 and IL-1 signalling. The changes in serum proteins upon remission differed between cluster 1 and 2.Patients with cranial GCA were characterized by altered endothelial and Th17 signalling, whereas patients not responding to treatment within the GUSTO-trial showed increased Th1 and diminished B cell signalling. Patients with anterior ischaemic optic neuropathy displayed higher levels of CHI3L1 (YKL40) and MMP12, and reduced levels of TIMP3.

Conclusion: Protein profiling identified patient clusters in GCA with distinct proteomic features and therefore likely different pathophysiology. These unique proteomic footprints might lead to more targeted treatments in future.

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血清蛋白分析揭示了巨细胞动脉炎患者的独特群集。

目的：我们研究了血清蛋白区分巨细胞动脉炎（GCA）患者临床和分子亚型的潜力：我们研究了血清蛋白区分巨细胞动脉炎（GCA）患者临床亚型和分子亚型的潜力：方法：使用邻近延伸测定法分析新发 GCA 患者（16 例）和获得缓解的患者（13 例）血清样本中的 1463 种蛋白质。进行了无监督和有监督聚类分析：无监督聚类分析根据蛋白质特征确定了三个不同的群组。与第2组相比，第1组患者的多发性风湿痛症状较轻，巨噬细胞迁移抑制因子（MIF）水平升高，NF-kB、STAT5和白细胞介素-1信号明显。第 1 组和第 2 组患者缓解后血清蛋白的变化有所不同。颅内 GCA 患者的特点是内皮细胞和 Th17 信号改变，而对 GUSTO 试验治疗无反应的患者则表现为 Th1 信号增强，B 细胞信号减弱。前部缺血性视神经病变患者的CHI3L1（YKL40）和MMP12水平较高，而TIMP3水平较低：蛋白质图谱分析发现，GCA 患者群具有不同的蛋白质组特征，因此可能具有不同的病理生理学特征。这些独特的蛋白质组学特征可能会在未来带来更有针对性的治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Rheumatology 医学-风湿病学

CiteScore

9.40

自引率

7.30%

发文量

1091

审稿时长

2 months

期刊介绍： Rheumatology strives to support research and discovery by publishing the highest quality original scientific papers with a focus on basic, clinical and translational research. The journal’s subject areas cover a wide range of paediatric and adult rheumatological conditions from an international perspective. It is an official journal of the British Society for Rheumatology, published by Oxford University Press. Rheumatology publishes original articles, reviews, editorials, guidelines, concise reports, meta-analyses, original case reports, clinical vignettes, letters and matters arising from published material. The journal takes pride in serving the global rheumatology community, with a focus on high societal impact in the form of podcasts, videos and extended social media presence, and utilizing metrics such as Altmetric. Keep up to date by following the journal on Twitter @RheumJnl.