Abstract
BackgroundThe 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.Methodsrs62324212 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.ResultsEnsembl 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).ConclusionIL21-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.
Highlights
Systemic lupus erythematosus (SLE) is an immunerelated disorder characterized by dysfunctional immune responses, leading to a lack of tolerance to self-antigens and over-secretion of autoantibodies
The single nucleotide polymorphism (SNP) rs62324212 was located within the long non-coding RNA (lncRNA) IL21-AS1, and the nearby genes were IL21 and IL2 (Fig. 1A)
Expression of IL21‐AS1 is reduced in patients with systemic lupus erythematosus (SLE) We evaluated the expression levels of three lncRNAs, including IL21-AS1 and IFNG Antisense RNA 1 (IFNG-AS1), in the Peripheral blood mononuclear cells (PBMCs) of healthy donors (HD) and patients with rheumatoid arthritis (RA) and SLE
Summary
Systemic lupus erythematosus (SLE) is an immunerelated disorder characterized by dysfunctional immune responses, leading to a lack of tolerance to self-antigens and over-secretion of autoantibodies. Hao et al Arthritis Research & Therapy (2021) 23:302 cells leads to a variety of autoimmune diseases through the accumulation of autoantibodies. Fine-tuning of the imbalance of Tfh and Tfr cells would develop new treatment strategies, such as a low-dose IL-2 therapy, but the underlying mechanisms of this imbalance remain unclear. Single nucleotide polymorphisms (SNPs) are primarily associated with SLE and other autoimmune diseases by altering the gene function and phenotype, and approximately 90% of SNPs are located in non-coding regions [5, 6]. 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
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