First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu, 807-8555, Japan.
Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Arthritis Res Ther. 2021 Dec 11;23(1):302. doi: 10.1186/s13075-021-02682-w.
The single nucleotide polymorphism (SNP) rs62324212, located in IL21 antisense RNA 1 (IL21-AS1), has been identified as a genetic risk variant associated with systemic lupus erythematosus (SLE). We aimed to probe the characteristics of IL21-AS1 and explore its clinical relevance focusing on T helper subsets and disease activity in patients with SLE.
rs62324212 genotyping was determined using allelic discrimination by quantitative PCR. Gene expression in peripheral blood mononuclear cells and cell surface markers in CD4 T cells were analyzed using PCR and flow cytometry. The association among IL21-AS1, CD4 T cell subsets, and SLE disease activity was accessed.
Ensembl Genome Browser analysis revealed that rs62324212 (C>A) was located in the predicting enhancer region of IL21-AS1. IL21-AS1 was expressed in the nucleus of CD4 T and B cells, but its expression was decreased in patients with SLE. IL21-AS1 expression was positively correlated with mRNA levels of IL-2 but not IL-21, and it was associated with the proportion of activated T follicular regulatory (Tfr) cells. Furthermore, we observed a significant negative correlation between IL21-AS1 expression and disease activity in patients with SLE (n = 53, p < 0.05).
IL21-AS1 has an effect on disease activity through an involvement of IL-2-mediated activation of Tfr cells in SLE. Thus, targeting the IL21-AS1 may provide therapeutic approaches for SLE.
位于白细胞介素 21 反义 RNA 1（IL21-AS1）的单核苷酸多态性（SNP）rs62324212 已被确定为与系统性红斑狼疮（SLE）相关的遗传风险变异。我们旨在探讨 IL21-AS1 的特征，并重点关注 T 辅助细胞亚群和 SLE 患者的疾病活动，探讨其临床相关性。
使用定量 PCR 的等位基因鉴别法确定 rs62324212 基因分型。使用 PCR 和流式细胞术分析外周血单个核细胞中的基因表达和 CD4 T 细胞表面标志物。评估 IL21-AS1、CD4 T 细胞亚群与 SLE 疾病活动之间的关系。
Ensembl 基因组浏览器分析表明，rs62324212（C>A）位于 IL21-AS1 的预测增强子区域。IL21-AS1 在 CD4 T 和 B 细胞的细胞核中表达，但在 SLE 患者中表达降低。IL21-AS1 表达与 IL-2 的 mRNA 水平呈正相关，而与 IL-21 无关，与激活的滤泡辅助 T 细胞（Tfr）的比例相关。此外，我们观察到 SLE 患者中 IL21-AS1 表达与疾病活动之间存在显著负相关（n=53，p<0.05）。
IL21-AS1 通过影响 IL-2 介导的 Tfr 细胞的激活对 SLE 的疾病活动产生影响。因此，针对 IL21-AS1 可能为 SLE 提供治疗方法。
