DNA methylation and transcriptome signature of the IL12B gene in ankylosing spondylitis

Ankylosing spondylitis (AS) is an autoimmune disease without a reliable biomarker. This study investigated the IL12B gene methylation as a robust marker by integrating DNA methylation and mRNA data.

A two-stage design was used for methylome and transcriptome investigation. The first phase detected methylation level from 99 AS patients and 99 healthy controls (HCs) whilst the second phase measured mRNA level from 20 patients and 20 HCs. We conducted analysis of differential methylation sites and receiver operating characteristic (ROC) as well as mRNA level to verify methylation.

We investigated 37 methylation sites that were mapped to 2 CpG islands (IL12B-1 and IL12B-2). Compared with HCs, the two islands were hypermethylated (IL12B-1: P = 4.6 ∗ 10 ^ -4; IL12B-2: P = 1.3 ∗ 10 ^ -5) and the mRNA level was overexpressed (P = 0.004) in AS patients. The subgroup analysis results showed a significant hypermethylation of the two islands in B27 positive group (IL12B-1: P = 3.7 ∗ 10 ^ -4; IL12B-2: P = 3.7 ∗ 10 ^ -6) and in male patients (IL12B-1: P = 4.9 ∗ 10 ^ -4; IL12B-2: P = 7.2 ∗ 10 ^ -6). ROC results found that the IL12B-1 island had a sensitivity of 62.6% and a specificity of 66.7%, and the IL12B-2 had a sensitivity of 50.0% and a specificity of 77.7%.

DNA methylation and transcriptome signature of the IL12B gene can discriminate AS patients from HCs, and hypermethylation of the IL12B may contribute to the pathogenesis of AS.