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

Abstract

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 TNFα (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 estimatesgood treatment outcomes in RA patients. K E Y W O R D Sdisease features, HDAC4, rheumatoid arthritis, treatment remission, treatment response Rheumatoid arthritis (RA), one of the top prevalent autoimmune and inflammatory diseases, affects nearly 1% population, especially elder women over the world. 1,2 Aberrant autoantibody, elevated systemic inflammation, symmetrical polyarthritis, and bone erosion are the main manifestations of RA. 3,4 Apart from them, RA patients also suffer from other complications, including cardiovascular injury, interstitial lung disease, neurological abnormalities, etc., [5][6][7] which make RA treatment even more challenging. Although novel drugs and treatment strategies are developed, there exists a nonnegligible proportion of RA patients who fail to respond or easily flare. 8,9 Therefore, potential marker exploration for RA supervision and treatment outcome prediction is valid for personalized medicine. 10 Histone deacetylase 4 (HDAC4), an essential member of histone deacetylase (HDAC), is initially observed to modify chondrogenesis, osteoblast differentiation, neural survival, etc. 11 Recently, HDAC4 is also honored to regulate immunity and inflammation, so as to be closely involved in the pathogenesis of immune/inflammation-related diseases. [12][13][14][15] In the aspect of RA, HDAC4 a...

Expressions of Peptidoglycan Recognition Protein 1, Neuron Towards Axon Guidance Factor-1 and miR-142-3p and Their Correlations in Patients with Rheumatoid Arthritis

“…Therefore, researchers have endeavored to clarify the pathogenesis and treatment targets of rheumatoid arthritis using molecular biology and serum index tests. 20 , 21 …”

“…Therefore, researchers have endeavored to clarify the pathogenesis and treatment targets of rheumatoid arthritis using molecular biology and serum index tests. 20,21 The level of PGLYRP-1 is strongly associated with the development and progression of atherosclerosis, 22,23 but its correlation with the development and progression of rheumatoid arthritis has rarely been reported. In this study, the PGLYRP-1 level was higher in the patients with rheumatoid arthritis, so PGLYRP-1 may participate in the development and progression of rheumatoid arthritis.…”