Relations between surface expression of the interleukin-2 receptor and release of the soluble form of the receptor in cultured mononuclear cells from patients with rheumatoid arthritis or systemic lupus erythematosus

Abstract Background 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. Methods 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. Results 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). Conclusion 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.

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Surface expression of heat shock protein 90 by blood mononuclear cells from patients with systemic lupus erythematosus

Journal of Autoimmunity ◽

10.1016/0896-8411(92)90194-u ◽

1992 ◽

Vol 5 (6) ◽

pp. 803-814 ◽

Cited By ~ 42

Author(s):

Feza M. Erkeller-Yüksel ◽

David A. Isenberg ◽

Veena B. Dhillon ◽

David S. Latchman ◽

Peter M. Lydyard

Keyword(s):

Systemic Lupus Erythematosus ◽

Heat Shock ◽

Heat Shock Protein ◽

Lupus Erythematosus ◽

Mononuclear Cells ◽

Heat Shock Protein 90 ◽

Surface Expression ◽

Systemic Lupus ◽

Blood Mononuclear Cells

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Involvement of lncRNA IL21-AS1 in Interleukin-2 and T Follicular Regulatory Cell Activation in Systemic Lupus Erythematosus

10.21203/rs.3.rs-885741/v1 ◽

2021 ◽

Author(s):

He Hao ◽

Shingo Nakayamada ◽

Naoaki Ohkubo ◽

Kaoru Yamagata ◽

Mingzeng Zhang ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Cell Activation ◽

Mononuclear Cells ◽

Interleukin 2 ◽

T Cell Subsets ◽

Mrna Levels ◽

Systemic Lupus ◽

Allelic Discrimination

Abstract Background 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 T helper subsets and disease activity in patients with SLE. Methods 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 were accessed. Results 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). Conclusion IL21-AS1 has an effect on disease activity through an impairment of IL-2-mediated activation of Tfr cell in SLE. Thus, targeting the IL21-AS1 may provide therapeutic approaches for SLE.

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