Gomez-Moreno Mariela, Ramos-González Elsy Janet, Castañeda-Delgado Julio Enrique, Castillo-Ortiz José Dionicio, Ramos-Remus Cesar, Zapata-Zúñiga Martin, Méndez J Alfredo, Monsiváis-Urenda Adriana, Portales-Pérez Diana Patricia, Enciso-Moreno José Antonio, Bastián Yadira
Unidad de Investigación Biomédica de Zacatecas, IMSS, Mexico; Facultad de Medicina, Universidad Autónoma de San Luis Potosí, Mexico.
Unidad de Investigación Biomédica de Zacatecas, IMSS, Mexico.
Hum Immunol. 2020 Dec;81(12):726-731. doi: 10.1016/j.humimm.2020.07.003. Epub 2020 Jul 18.
The first degree relatives of rheumatoid arthritis (RA) patients have a higher risk of developing RA, which is related to the expression of autoantibodies against citrullinated proteins (ACPA). Remarkably, prior to the onset of RA, cartilage damage is already initiated, whereas ACPA autoantibodies are already expressed. Here we show that both TNF-α and IL-6 are also increased prior to the onset of RA. Furthermore, when the levels of DKK1 and Sclerostin were evaluated in first degree relatives of RA patients, we found that the serum levels of TNF- α correlate with the expression levels of both DKK1 and Sclerostin. Interestingly, when the disease is already established, the correlation of TNF- α with DKK1 is lost in RA patients, whereas the correlation of Sclerostin with both TNF- α and IL-6 is further increased. Our data suggest a subclinical inflammation in patients at high risk of developing RA, which might lead to an increase in the levels of both DKK1 and Sclerostin, contributing to joint damage in the preclinical phase of the disease linked to the expression of ACPA autoantibodies.
类风湿关节炎（RA）患者的一级亲属患RA的风险更高，这与抗瓜氨酸化蛋白自身抗体（ACPA）的表达有关。值得注意的是，在RA发病之前，软骨损伤就已经开始，而ACPA自身抗体也已表达。我们在此表明，在RA发病之前，TNF-α和IL-6水平也会升高。此外，当评估RA患者一级亲属中DKK1和硬化蛋白的水平时，我们发现TNF-α的血清水平与DKK1和硬化蛋白的表达水平相关。有趣的是，当疾病已经确诊时，RA患者中TNF-α与DKK1的相关性消失，而硬化蛋白与TNF-α和IL-6的相关性进一步增强。我们的数据表明，有发展为RA高风险的患者存在亚临床炎症，这可能导致DKK1和硬化蛋白水平升高，在与ACPA自身抗体表达相关的疾病临床前期阶段造成关节损伤。
