Restoration of Overexpressed Variable Heavy Chain 2 Transcripts with Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis

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.

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

Kim

Yoon

Song

et al. 2017

Autoimmunity

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Restoration of Overexpressed Variable Heavy Chain 2 Transcripts with Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis

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

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

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