Serum HDAC4 level in rheumatoid arthritis: Longitudinal change during treatment and correlation with clinical outcomes

Objective Histone deacetylase 4 (HDAC4) modulates immunity, inflammation, and osteoblast differentiation to engage in rheumatoid arthritis (RA) etiology. This study aimed to evaluate the HDAC4 longitudinal change and its relationship with clinical features and outcomes in RA patients. Methods Eighty‐three RA patients were enrolled. Their serum HDAC4 level was detected by ELISA at baseline (W0), week (W) 4, W12, and W24 after treatment. RA patients were divided into response or non‐response, low disease activity (LDA) or non‐LDA, remission or non‐remission patients according to their treatment outcomes at W24. Meanwhile, serum HDAC4 was detected by ELISA in 20 osteoarthritis patients and 20 healthy controls (HCs). Results HDAC4 level was reduced in RA patients compared with HCs ( p  < 0.001) and osteoarthritis patients ( p  = 0.009). HDAC4 was negatively related to some of the disease activity indexes such as C‐reactive protein ( p  = 0.003), tender joint count ( p  = 0.025), and disease activity score based on 28 joints ( p  = 0.013) in RA patients; it was also negatively correlated with TNF‐α ( p  = 0.003), IL‐6 ( p  = 0.022), and IL‐17A ( p  = 0.015). However, the HDAC4 level was not related to different treatment histories or current initiating treatment regimens (all p  < 0.05). After treatment, HDAC4 was gradually elevated along with the time ( p  < 0.001). Interestingly, HDAC4 level at W12 ( p  = 0.041) and W24 ( p  = 0.012) was higher in response patients versus non‐response patients, and its level at W24 was higher in LDA patients versus non‐LDA patients ( p  = 0.019), and in remission patients versus non‐remission patients ( p  = 0.039). Conclusion HDAC4 gradually increases during treatment and its elevation estimates good treatment outcomes in RA patients.