Rheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, Spain.
Scientific department, Cobiomic Bioscience S.L, Cordoba, Spain.
Front Immunol. 2024 Feb 14;15:1333995. doi: 10.3389/fimmu.2024.1333995. eCollection 2024.
RA patients are at higher risk of cardiovascular disease, influenced by therapies. Studying their cardiovascular and cardiometabolic proteome can unveil biomarkers and insights into related biological pathways.
This study included two cohorts of RA patients: newly diagnosed individuals (n=25) and those with established RA (disease duration >25 years, n=25). Both cohorts were age and sex-matched with a control group (n=25). Additionally, a longitudinal investigation was conducted on a cohort of 25 RA patients treated with methotrexate and another cohort of 25 RA patients treated with tofacitinib for 6 months. Clinical and analytical variables were recorded, and serum profiling of 184 proteins was performed using the Olink technology platform.
RA patients exhibited elevated levels of 75 proteins that might be associated with cardiovascular disease. In addition, 24 proteins were increased in RA patients with established disease. Twenty proteins were commonly altered in both cohorts of RA patients. Among these, elevated levels of CTSL1, SORT1, SAA4, TNFRSF10A, ST6GAL1 and CCL18 discriminated RA patients and HDs with high specificity and sensitivity. Methotrexate treatment significantly reduced the levels of 13 proteins, while tofacitinib therapy modulated the expression of 10 proteins. These reductions were associated with a decrease in DAS28. Baseline levels of SAA4 and high levels of BNP were associated to the non-response to methotrexate. Changes in IL6 levels were specifically linked to the response to methotrexate. Regarding tofacitinib, differences in baseline levels of LOX1 and CNDP1 were noted between non-responder and responder RA patients. In addition, response to tofacitinib correlated with changes in SAA4 and TIMD4 levels.
In summary, this study pinpoints molecular changes linked to cardiovascular disease in RA and proposes candidate protein biomarkers for distinguishing RA patients from healthy individuals. It also highlights how methotrexate and tofacitinib impact these proteins, with distinct alterations corresponding to each drug's response, identifying potential candidates, as SAA4, for the response to these therapies.
类风湿关节炎（RA）患者心血管疾病风险较高，这受到治疗方法的影响。研究其心血管和心脏代谢蛋白质组可以揭示生物标志物，并深入了解相关的生物学途径。
本研究纳入了两组 RA 患者：新诊断患者（n=25）和已确诊 RA 患者（病程>25 年，n=25）。两组均与对照组（n=25）进行年龄和性别匹配。此外，对 25 名接受甲氨蝶呤治疗的 RA 患者和 25 名接受托法替尼治疗 6 个月的 RA 患者进行了纵向研究。记录了临床和分析变量，并使用 Olink 技术平台对 184 种蛋白质进行了血清分析。
RA 患者表现出 75 种可能与心血管疾病相关的蛋白质水平升高。此外，已确诊 RA 患者中有 24 种蛋白质水平升高。两组 RA 患者中有 20 种蛋白质共同改变。其中，CTSL1、SORT1、SAA4、TNFRSF10A、ST6GAL1 和 CCL18 的水平升高可区分 RA 患者和健康对照者，具有高特异性和敏感性。甲氨蝶呤治疗显著降低了 13 种蛋白质的水平，而托法替尼治疗调节了 10 种蛋白质的表达。这些降低与 DAS28 的降低相关。SAA4 的基线水平和 BNP 的高水平与甲氨蝶呤的无反应相关。IL6 水平的变化与甲氨蝶呤的反应具体相关。关于托法替尼，无反应和有反应的 RA 患者之间在 LOX1 和 CNDP1 的基线水平上存在差异。此外，托法替尼的反应与 SAA4 和 TIMD4 水平的变化相关。
总之，本研究确定了 RA 与心血管疾病相关的分子变化，并提出了区分 RA 患者和健康个体的候选蛋白质生物标志物。它还强调了甲氨蝶呤和托法替尼对这些蛋白质的影响，每种药物的反应都有不同的改变，确定了潜在的候选者，如 SAA4，作为对这些治疗的反应。
