Divergent gene signatures and neutrophil enrichment in lymph nodes of inflammatory arthritis patients

IF 4.9 2区医学 Q1 Medicine

Arthritis Research & Therapy Pub Date : 2025-04-23 DOI:10.1186/s13075-025-03557-0

Aoife M. O’Byrne, Janne W. Bolt, Chaja M.J. van Ansenwoude, Martijn van der Heijde, Johanna F. Semmelink, Aldo Jongejan, Perry D. Moerland, Mario Maas, Marleen G.H. van de Sande, Lisa G.M. van Baarsen

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引用次数: 0

Abstract

Lymph node (LN) studies in anti-cyclic citrullinated protein antibodies (ACPA) positive rheumatoid arthritis (RA) patients have revealed notable alterations in adaptive immune cell populations. However, it remains unclear whether similar changes occur in seronegative inflammatory arthritis, such as psoriatic arthritis (PsA) or ACPA-negative RA. This study investigates molecular and cellular alterations in LN biopsies from ACPA-positive RA patients, ACPA-negative inflammatory arthritis (IA) patients, and healthy controls (HCs). Ultrasound-guided LN biopsies were collected from 25 HCs, 14 ACPA positive RA patients and 45 ACPA negative IA patients (including various IA subtypes). Whole LN tissue biopsies were analyzed by transcriptome analyses, quantitative PCR and immunohistochemistry. Distinct LN gene expression profiles were identified in ACPA-positive RA and ACPA-negative IA patients compared to HCs. ACPA-positive RA patients exhibited upregulation of genes associated with adaptive immunity, while ACPA-negative IA patients showed higher expression of genes related to innate immune cell function. Subsequent qPCR analysis confirmed increased mRNA expression of Cathepsin G, a serine protease highly expressed by neutrophils, in ACPA negative IA patients. Immunohistochemistry demonstrated significantly elevated CD15 + neutrophil presence in LNs from IA patients compared to HCs, irrespective of ACPA status and diagnosis (RA or PsA). This study provides novel insights into the immune landscape of lymph nodes in inflammatory arthritis, emphasizing an unexpected role for neutrophils in IA patients. Future research should explore the functional implications of neutrophils within these uninfected lymph nodes to better understand their contribution to the pathogenesis of inflammatory arthritis.

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炎性关节炎患者淋巴结中不同基因特征和中性粒细胞富集

对抗环瓜氨酸蛋白抗体（ACPA）阳性类风湿性关节炎（RA）患者淋巴结（LN）的研究显示，适应性免疫细胞群发生了显著变化。然而，血清阴性炎症性关节炎（如银屑病关节炎（PsA）或 ACPA 阴性 RA）是否也会发生类似的变化仍不清楚。本研究调查了ACPA阳性RA患者、ACPA阴性炎症性关节炎（IA）患者和健康对照组（HCs）LN活检组织的分子和细胞变化。从 25 名健康对照者、14 名 ACPA 阳性 RA 患者和 45 名 ACPA 阴性 IA 患者（包括各种 IA 亚型）中收集了超声引导下的 LN 活检组织。通过转录组分析、定量 PCR 和免疫组化对整个 LN 组织活检进行了分析。与 HCs 相比，ACPA 阳性 RA 和 ACPA 阴性 IA 患者的 LN 基因表达谱有所不同。ACPA阳性的RA患者表现出与适应性免疫相关基因的上调，而ACPA阴性的IA患者则表现出与先天性免疫细胞功能相关基因的高表达。随后的 qPCR 分析证实，在 ACPA 阴性的 IA 患者中，中性粒细胞高度表达的丝氨酸蛋白酶 Cathepsin G 的 mRNA 表达增加。免疫组化显示，与中性粒细胞相比，IA 患者的 LN 中 CD15 + 中性粒细胞明显增多，与 ACPA 状态和诊断（RA 或 PsA）无关。这项研究为了解炎症性关节炎淋巴结的免疫状况提供了新的视角，强调了中性粒细胞在IA患者中的意外作用。未来的研究应探索中性粒细胞在这些未感染淋巴结中的功能影响，以更好地了解它们对炎症性关节炎发病机制的贡献。

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

Arthritis Research & Therapy RHEUMATOLOGY-

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.