Centre for Bone and Arthritis Research, Institute of Medicine, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Krefting Research Center, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
PLoS One. 2021 Mar 26;16(3):e0249205. doi: 10.1371/journal.pone.0249205. eCollection 2021.
Rheumatoid arthritis (RA) is associated with development of generalized osteoporosis. Bone-degrading osteoclasts are derived from circulating precursor cells of monocytic lineage, and the intermediate monocyte population is important as osteoclast precursors in inflammatory conditions. T cells of various subsets are critical in the pathogenesis of both RA and associated osteoporosis, but so far, no studies have examined associations between circulating intermediate monocytes, T cell subsets and bone characteristics in patients with RA. The aim of this study was to investigate the frequency of intermediate monocytes in patients with untreated early rheumatoid arthritis (ueRA) compared to healthy controls (HC), and to explore the correlation between intermediate monocytes and a comprehensive panel of T helper cell subsets, bone density and bone microarchitecture in ueRA patients.
78 patients with ueRA fulfilling the ACR/EULAR 2010 criteria were included and compared to 29 age- and sex-matched HC. Peripheral blood samples were obtained before start of treatment and proportions of monocyte subsets and CD4+ helper and regulatory T cell subsets were analyzed by flow cytometry. Bone densitometry was performed on 46 of the ueRA patients at inclusion using DXA and HR-pQCT.
Flow cytometric analyses showed that the majority of ueRA patients had frequencies of intermediate monocytes comparable to HC. The intermediate monocyte population correlated positively with CXCR3+ Th17 cells in ueRA patients but not in HC. However, neither the proportions of intermediate monocytes nor CXCR3+ Th17 cells were associated with bone density or bone microarchitecture measurements.
Our findings suggest that in early RA, the intermediate monocytes do not correlate with bone characteristics, despite positive correlation with circulating CXCR3+ Th17 cells. Future longitudinal studies in patients with longer disease duration are required to fully explore the potential of intermediate monocytes to drive bone loss in RA.
类风湿关节炎（RA）与全身性骨质疏松症的发展有关。破骨细胞来源于单核细胞谱系的循环前体细胞，而中间单核细胞群体作为炎症条件下的破骨细胞前体很重要。各种亚群的 T 细胞在 RA 和相关骨质疏松症的发病机制中都很关键，但迄今为止，尚无研究检查 RA 患者循环中间单核细胞、T 细胞亚群与骨特征之间的相关性。本研究旨在比较未经治疗的早期类风湿关节炎（ueRA）患者与健康对照（HC）之间中间单核细胞的频率，并探讨中间单核细胞与辅助性 T 细胞亚群综合面板、ueRA 患者的骨密度和骨微结构之间的相关性。
纳入 78 例符合 ACR/EULAR 2010 标准的 ueRA 患者，并与 29 名年龄和性别匹配的 HC 进行比较。在开始治疗前采集外周血样，通过流式细胞术分析单核细胞亚群和 CD4+辅助和调节性 T 细胞亚群的比例。对 46 例 ueRA 患者在纳入时进行骨密度测定，采用 DXA 和 HR-pQCT。
流式细胞术分析显示，大多数 ueRA 患者的中间单核细胞频率与 HC 相似。ueRA 患者的中间单核细胞群体与 CXCR3+Th17 细胞呈正相关，但在 HC 中则没有。然而，中间单核细胞的比例或 CXCR3+Th17 细胞与骨密度或骨微结构测量均无关。
我们的研究结果表明，在早期 RA 中，尽管与循环 CXCR3+Th17 细胞呈正相关，但中间单核细胞与骨特征无关。需要对疾病持续时间较长的患者进行前瞻性纵向研究，以充分探索中间单核细胞在 RA 中导致骨丢失的潜力。
