Youssef Soha R, Hassan Esraa H, Morad Caroline S, Elazab Elged Adel A, El-Gamal Rasha A
Clinical Pathology Department, Ain Shams University, Cairo, Egypt.
Regional Blood Transfusion Center, Cairo, Egypt.
J Inflamm Res. 2021 Sep 7;14:4445-4455. doi: 10.2147/JIR.S327465. eCollection 2021.
Erythroferrone (ERFE) is well acknowledged for its inhibitory function on hepcidin synthesis in the liver during stress erythropoiesis, thereby ensuring sufficient iron supply to bone marrow erythroblasts. Hepcidin plays an indispensable role in the pathogenesis of anemia of chronic disease (ACD). Thus, ERFE was suggested to protect against ACD in various diseases. Rheumatoid arthritis (RA) is commonly involved with ACD and high hepcidin levels, with a further increase of the latter in active states. The present study is a case-control study that aimed to determine the pattern of ERFE expression in RA patients with concomitant ACD and study its relationship with hepcidin, erythropoietin (EPO) and disease activity.
Fifty-five RA patients with ACD were categorized into active and inactive RA using the disease activity score (DAS28); 15 healthy subjects were included as control subjects. ERFE was measured for patients and control subjects using quantitative real-time polymerase chain reaction, in addition to testing for CBC, ESR, CRP, iron profile parameters and hepcidin. EPO was assessed for patients of both active and inactive RA groups.
ERFE and hepcidin showed the highest levels in active RA; ERFE values were similar in control subjects and inactive RA patients, while hepcidin was significantly higher in inactive RA than control subjects. Patients with high ERFE levels had higher RBC, Hct, MCV, hepcidin and EPO levels. Stepwise regression analysis has identified DAS28 and disease duration as the best predictors of ERFE values, whereas ERFE and hepcidin were independent predictors of disease activity.
We introduce ERFE as a novel marker of RA activity. Although the inhibitory effect of ERFE on hepcidin is not evident, our results still indicate that ERFE may have a beneficial erythropoietic effect in the context of ACD in RA disease activity.
促红细胞生成素铁（ERFE）因其在应激性红细胞生成过程中对肝脏中血浆铁调素合成的抑制作用而广为人知，从而确保向骨髓成红细胞提供充足的铁供应。血浆铁调素在慢性病贫血（ACD）的发病机制中起不可或缺的作用。因此，有人提出ERFE可预防各种疾病中的ACD。类风湿关节炎（RA）常伴有ACD和高血浆铁调素水平，且在活动期后者会进一步升高。本研究是一项病例对照研究，旨在确定合并ACD的RA患者中ERFE的表达模式，并研究其与血浆铁调素、促红细胞生成素（EPO）及疾病活动度的关系。
55例合并ACD的RA患者根据疾病活动评分（DAS28）分为活动期和非活动期RA；纳入15名健康受试者作为对照。除检测全血细胞计数、红细胞沉降率、C反应蛋白、铁代谢参数和血浆铁调素外，还采用定量实时聚合酶链反应检测患者和对照的ERFE。对活动期和非活动期RA组的患者均评估EPO。
ERFE和血浆铁调素在活动期RA中水平最高；对照和非活动期RA患者的ERFE值相似，而非活动期RA患者的血浆铁调素显著高于对照。ERFE水平高的患者红细胞、血细胞比容、平均红细胞体积、血浆铁调素和EPO水平更高。逐步回归分析确定DAS28和病程是ERFE值的最佳预测指标，而ERFE和血浆铁调素是疾病活动度的独立预测指标。
我们将ERFE作为RA活动度的一种新标志物。尽管ERFE对血浆铁调素的抑制作用不明显，但我们的结果仍表明，在RA疾病活动的ACD背景下，ERFE可能具有有益的促红细胞生成作用。
