Natural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung, Republic of Korea.
Department of Marine Bio Food Science, Gangneung-Wonju National University, Gangneung, Republic of Korea.
Front Immunol. 2024 May 3;15:1410365. doi: 10.3389/fimmu.2024.1410365. eCollection 2024.
Seronegative rheumatoid arthritis (RA) is defined as RA without circulating autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies; thus, early diagnosis of seronegative RA can be challenging. Here, we aimed to identify diagnostic biomarkers for seronegative RA by performing lipidomic analyses of sera and urine samples from patients with RA.
We performed untargeted lipidomic analysis of sera and urine samples from 111 RA patients, 45 osteoarthritis (OA) patients, and 25 healthy controls (HC). These samples were divided into a discovery cohort (n = 97) and a validation cohort (n = 84). Serum samples from 20 patients with systemic lupus erythematosus (SLE) were also used for validation.
The serum lipidome profile of RA was distinguishable from that of OA and HC. We identified a panel of ten serum lipids and three urine lipids in the discovery cohort that showed the most significant differences. These were deemed potential lipid biomarker candidates for RA. The serum lipid panel was tested using a validation cohort; the results revealed an accuracy of 79%, a sensitivity of 71%, and a specificity of 86%. Both seropositive and seronegative RA patients were differentiated from patients with OA, SLE, and HC. Three urinary lipids showing differential expression between RA from HC were identified with an accuracy of 84%, but they failed to differentiate RA from OA. There were five lipid pathways that differed between seronegative and seropositive RA.
Here, we identified a panel of ten serum lipids as potential biomarkers that can differentiate RA from OA and SLE, regardless of seropositivity. In addition, three urinary lipids had diagnostic utility for differentiating RA from HC.
血清阴性类风湿关节炎（RA）是指无循环自身抗体（如类风湿因子和抗瓜氨酸蛋白抗体）的 RA；因此，血清阴性 RA 的早期诊断具有挑战性。在这里，我们通过对 RA 患者的血清和尿液样本进行脂质组学分析，旨在确定血清阴性 RA 的诊断生物标志物。
我们对 111 例 RA 患者、45 例骨关节炎（OA）患者和 25 例健康对照者（HC）的血清和尿液样本进行了非靶向脂质组学分析。这些样本分为发现队列（n = 97）和验证队列（n = 84）。还使用 20 例系统性红斑狼疮（SLE）患者的血清样本进行验证。
RA 的血清脂质组谱与 OA 和 HC 不同。我们在发现队列中确定了一组十个血清脂质和三个尿液脂质，它们显示出最显著的差异。这些被认为是 RA 的潜在脂质生物标志物候选物。使用验证队列测试了血清脂质组；结果显示准确率为 79%，灵敏度为 71%，特异性为 86%。血清阳性和血清阴性 RA 患者均与 OA、SLE 和 HC 患者区分开来。在 RA 与 HC 之间差异表达的三个尿液脂质被鉴定出准确率为 84%，但未能区分 RA 与 OA。有五个脂质途径在血清阴性和血清阳性 RA 之间存在差异。
在这里，我们确定了一组十个血清脂质作为潜在的生物标志物，可以区分 RA 与 OA 和 SLE，无论血清阳性与否。此外，三个尿液脂质对区分 RA 与 HC 具有诊断效用。
