Alterations and abnormal expression of A20 in peripheral monocyte subtypes in patients with rheumatoid arthritis

As the precursors of macrophages and osteoclasts, monocytes play an important role in the pathogenesis of rheumatoid arthritis (RA). Since the deficiency of zinc-finger protein A20 in myeloid cells triggers erosive polyarthritis resembling RA, A20 in monocytes may play a protective role in RA. In the present study, we aimed to investigate the abnormality of monocyte subtypes and the expression of zinc-finger protein A20 in RA. Peripheral blood mononuclear cells and clinical data were collected from RA patients and healthy controls (HCs). Monocyte subtypes and A20 expression were determined through flow cytometry and compared between the two groups. Correlations between monocyte subtypes, A20 expression, and clinical data were analyzed. A total of 43 RA patients and 23 HCs were included in the present study. RA patients had higher absolute monocyte counts (p < 0.001) in the peripheral blood. The proportions and counts of intermediate monocytes (IMs) (both p < 0.001) and non-classical monocytes (NCMs) were higher (both p < 0.001) in RA patients. The expression of A20 in IMs (p < 0.001) was lower in RA patients compared with that in the HCs. Furthermore, the expression of A20 in IMs was negatively correlated with the anti-cyclic citrullinated peptide (CCP) antibody level in RA patients (r = - 0.409, p = 0.01). The expression of A20 in NCMs was positively correlated with modified total Sharp score (mTSS) in RA patients (r = 0.471, p = 0.02). Collectively, we proved that IMs and NCMs were increased in RA patients, suggesting that they played a suggestive role in the pathogenesis of RA. Furthermore, the downregulation of A20 in IMs might be correlated with anti-CCP antibody production. The A20 expression in NCMs might affect bone erosion in RA. Key Points • IMs and NCMs were increased in the peripheral blood of RA patients, suggesting their pathogenic role in RA. • The decreased expression of zinc-finger protein A20 in IMs of RA patients suggested the protective role of A20 in RA. • The negative correlation between the A20 expression in IMs and anti-CCP antibody revealed that A20 in IMs might be related to the formation of anti-CCP antibodies. • The positive correlation between the A20 expression in NCMs and mTSS revealed that A20 in NCMs might affect the bone erosion in RA.