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.

类风湿性关节炎（RA）患者的一级亲属发生RA的风险较高，这与抗瓜氨酸蛋白（ACPA）自身抗体的表达有关。值得注意的是，在 RA 发作之前，软骨损伤已经开始，而 ACPA 自身抗体已经表达。在这里，我们显示 TNF-α 和 IL-6 在 RA 发作之前也增加。此外，当在 RA 患者的一级亲属中评估 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，当疾病已经确立时，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 的相关性进一步增加。