Pascual-García Sandra, Martínez-Peinado Pascual, López-Jaén Ana B, Navarro-Blasco Francisco J, Montoyo-Pujol Yoel G, Roche Enrique, Peiró Gloria, Sempere-Ortells José M
Department of Biotechnology, University of Alicante, 03690 San Vicente del Raspeig, Spain.
Rheumatology Unit, University General Hospital of Elche, 03203 Elche, Spain.
Int J Mol Sci. 2023 Aug 2;24(15):12351. doi: 10.3390/ijms241512351.
Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the most frequently used rheumatoid arthritis (RA) diagnostic markers, but they are unable to anticipate the patient's evolution or response to treatment. The aim of this study was to identify possible severity biomarkers to predict an upcoming flare-up or remission period. To address this objective, sera and anticoagulated blood samples were collected from healthy controls (HCs; n = 39) and from early RA (n = 10), flare-up (n = 5), and remission (n = 16) patients. We analyzed leukocyte phenotype markers, regulatory T cells, cell proliferation, and cytokine profiles. Flare-up patients showed increased percentages of cluster of differentiation (CD)3CD4 lymphocytes ( < 0.01) and granulocytes ( < 0.05) but a decreased natural killer (NK)/T lymphocyte ratio ( < 0.05). Analysis of leukocyte markers by principal component analysis (PCA) and receiver operating characteristic (ROC) curves showed that CD45RO ( < 0.0001) and CD45RA ( < 0.0001) B lymphocyte expression can discriminate between HCs and early RA patients, while CD3CD4 lymphocyte percentage ( < 0.0424) and CD45RA ( < 0.0424), CD62L ( < 0.0284), and CD11a ( < 0.0185) B lymphocyte expression can differentiate between flare-up and RA remission subjects. Thus, the combined study of these leukocyte surface markers could have potential as disease severity biomarkers for RA, whose fluctuations could be related to the development of the characteristic pro-inflammatory environment.
类风湿因子（RF）和抗瓜氨酸化蛋白抗体（ACPA）是类风湿关节炎（RA）最常用的诊断标志物，但它们无法预测患者的病情发展或对治疗的反应。本研究的目的是确定可能的严重程度生物标志物，以预测即将到来的病情发作或缓解期。为实现这一目标，我们收集了健康对照者（HCs；n = 39）以及早期RA患者（n = 10）、病情发作期患者（n = 5）和缓解期患者（n = 16）的血清和抗凝血液样本。我们分析了白细胞表型标志物、调节性T细胞、细胞增殖和细胞因子谱。病情发作期患者的分化簇（CD）3CD4淋巴细胞百分比（<0.01）和粒细胞百分比（<0.05）增加，但自然杀伤（NK）/T淋巴细胞比率降低（<0.05）。通过主成分分析（PCA）和受试者工作特征（ROC）曲线对白细胞标志物进行分析表明，CD45RO（<0.0001）和CD45RA（<0.0001）B淋巴细胞表达可区分HCs和早期RA患者，而CD3CD4淋巴细胞百分比（<0.0424）以及CD45RA（<0.0424）、CD62L（<0.0284）和CD11a（<0.0185）B淋巴细胞表达可区分病情发作期和RA缓解期患者。因此，这些白细胞表面标志物的联合研究可能具有作为RA疾病严重程度生物标志物的潜力，其波动可能与特征性促炎环境的发展有关。
