Expression of activation-induced cytidine deaminase splicing variants in patients with ankylosing spondylitis

Abstract

To investigate the expression patterns of activation-induced cytidine deaminase (AID) variants in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and examine their clinical implications, we isolated PBMCs from healthy controls (HC, n = 33) and patients with AS (n = 62), and measured mRNA expression of AID variants and translesion synthesis (TLS) polymerases using quantitative real-time polymerase chain reaction. The proportion of patients with AS in whom AID splicing variant (sv) 2 was expressed was significantly higher than that of HC (p = .031). 80.7% of AS patients were treated with tumour necrosis factor inhibitor (TNFi). Significantly higher proportion of the TNFi-treated group expressed sv2 compared to the TNF-naïve group (p = .037). And we compared the level of AID variants expression between the TNFi-treated group and the TNF-naïve group. The expression levels of AID full-length (FL) and sv1 were significantly lower in the TNFi-treated group than the TNF-naïve group (FL: p = .002, sv1: p = .045). In addition, we investigated mRNA expression levels of translesion synthesis (TLS) polymerases in PBMCs from patients with AS and HC. The expression level of TLS pol ι was significantly lower in patients with AS than in HC (p = .007). In conclusion, AS patients expressed significantly higher levels of sv2 than HC. TNFi treatment restored the gene expression of the AID variants (FL, sv1, and sv2) in patients with AS. A clear understanding of the underlying cellular and molecular mechanisms will help to identify the pathogenesis of AS better and to develop novel therapeutic targets.

Keywords:

• Ankylosing spondylitis
• activation-induced cytidine deaminase
• tumour necrosis factor inhibitors
• translesion synthesis polymerases
• autoimmune disease

Disclosure statement

All authors declare that they have no conflicts of interest.

Additional information

Funding

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (MEST) under Grant [grant number: NRF-2013R1A1A2013036 to S.-R.P.] and Grant [grant number: NRF-2016R1D1A3B03931646 to S.-C.S.].