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类风湿关节炎患者间质性肺病的血清学生物标志物的队列研究。

Cohort study of serological biomarkers for interstitial lung disease in patients with rheumatoid arthritis.

机构信息

Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden.

出版信息

Scand J Rheumatol. 2024 Nov;53(6):386-395. doi: 10.1080/03009742.2024.2413238. Epub 2024 Oct 25.

DOI:10.1080/03009742.2024.2413238
PMID:39450495
Abstract

OBJECTIVE

Interstitial lung disease (ILD) is an important cause of mortality in patients with rheumatoid arthritis (RA). Early RA-ILD detection is essential to improve prognosis. Here, we investigated eight serological biomarkers that may contribute to RA-ILD detection.

METHOD

Fifty-five patients from the Early Rheumatoid Arthritis Program were evaluated for ILD with high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) using the SCAPIS protocol. Blood samples were obtained for biomarker analysis, and patients' clinical records were reviewed. We defined ILD using five different models based on the measurements used to confirm ILD: Model A = HRCT; B = PFTs; C = A plus B; D = C plus symptoms; and E = D plus inhalations.

RESULTS

Among 55 patients, two had an ILD diagnosis before the study, but over one-third fulfilled the ILD criteria. Cancer antigen 15-3 (CA15-3) and matrix metalloproteinase-7 (MMP-7) differentiated between RA with and without ILD (all p < 0.05). Surfactant protein D (SP-D) showed similar trends, as did macrophage inflammatory protein-1β (MIP-1β) and chitinase 3-like protein-1 (YKL-40). Based on Pearson's correlation coefficients, MIP-1β and YKL-40 were significantly correlated with DAS28 (MIP-1β: 0.3; YKL-40: 0.4), ESR (MIP-1β: 0.3; YKL-40: 0.4), and CRP (only MIP-1β: 0.4) (all p < 0.05). CA15-3 was correlated with rheumatoid factor and anti-citrullinated peptide antibodies (Pearson's correlation 0.3; both p = 0.03).

CONCLUSIONS

CA15-3 was the most significant biomarker for ILD detection in RA patients with stable low disease activity, closely followed by MMP-7. SP-D, MIP-1β, and YKL-40 may also contribute to RA-ILD diagnosis.

摘要

目的

间质性肺病(ILD)是类风湿关节炎(RA)患者死亡的重要原因。早期 RA-ILD 的检测对于改善预后至关重要。在这里,我们研究了八个可能有助于 RA-ILD 检测的血清生物标志物。

方法

使用 SCAPIS 方案,对 55 名来自早期类风湿关节炎项目的患者进行高分辨率计算机断层扫描(HRCT)和肺功能测试(PFTs)评估ILD。采集血液样本进行生物标志物分析,并回顾患者的临床记录。我们根据用于确认ILD 的测量值定义了五种不同的ILD 模型:A 模型=HRCT;B 模型=PFTs;C 模型=A 加 B;D 模型=C 加症状;E 模型=D 加吸入物。

结果

在 55 名患者中,有两名在研究前被诊断为ILD,但超过三分之一的患者符合ILD 标准。癌抗原 15-3(CA15-3)和基质金属蛋白酶-7(MMP-7)可区分有和无ILD 的 RA(均 p<0.05)。表面活性剂蛋白 D(SP-D)也表现出类似的趋势,巨噬细胞炎症蛋白-1β(MIP-1β)和几丁质酶 3 样蛋白-1(YKL-40)也是如此。基于 Pearson 相关系数,MIP-1β 和 YKL-40 与 DAS28(MIP-1β:0.3;YKL-40:0.4)、ESR(MIP-1β:0.3;YKL-40:0.4)和 CRP(仅 MIP-1β:0.4)显著相关(均 p<0.05)。CA15-3 与类风湿因子和抗瓜氨酸肽抗体相关(Pearson 相关系数 0.3;均 p=0.03)。

结论

在疾病活动度稳定且较低的 RA 患者中,CA15-3 是ILD 检测最显著的生物标志物,紧随其后的是 MMP-7。SP-D、MIP-1β 和 YKL-40 也可能有助于 RA-ILD 的诊断。

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