The association of single nucleotide polymorphism of interleukin-21 gene and serum interleukin-21 levels with systemic lupus erythematosus

Ahmed, Yasmin; Erfan, Dina M.; Hafez, S; Shehata, Iman H; Morshedy, Nashwa Aly

doi:10.1016/j.ejmhg.2016.04.006

Cited by 6 publications

(5 citation statements)

References 29 publications

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“…22,23 Dolff et al 24 26 outlined that active SLE patients had 4-fold elevated IL-21 mRNA higher intracellular levels in peripheral blood CD4 + T cells compared to inactive SLE and HCs, but IL-21 receptor mRNA levels were equal in SLE and healthy controls. In contrast to our results, Pan et al 27 and Dolff et al 28 suggested that IL-21 level decreased in SLE patients compared to HCs with no significant difference in serum IL-21 between SLE patients with or without nephritis. This is may be due to new-onset SLE disease course in patients included in their studies.…”

Section: Discussioncontrasting

confidence: 99%

“…Our results revealed markedly higher serum IL-21 levels in active LN patients with a high SLEDAI and renal-SLEDAI, compared to those with a lower index score. In agreement with our observation, Ahmed et al 23 reported a statistical association between IL-21 concentration and SLEDAI in Egyptian SLE patients in addition to association between nephritis and serum IL-21 levels. In contrast to our results, Dolff et al 24 observed no association between the SLEDAI and IL-21 + T-cell proportions, the authors attributed these results to intrinsic variance and relatively few active cases in their study.…”

Section: Discussionsupporting

confidence: 93%

“…Our results revealed a significant upgrading of serum IL-21 level (420 pg/ml) during active LN compared to both HCs and inactive LN patients which was in consistence with previous studies that showed significantly higher IL-21 concentrations in SLE patients compared to control groups. 22,23 Dolff et al 24 suggested significant increase in percentage of IL-21 producing CD4 + T-cells and CD8 + T-cells in SLE than controls in relationship to IL-17A production. According to Jacquemin et al, 25 IL-21 signals worked along with OX40 protein signals to induce memory T-cell synthesis of CXCR5 and IL-21.…”

Section: Discussionmentioning

confidence: 99%

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The potential use of serum interleukin-21 as biomarker for lupus nephritis activity compared to cytokines of the tumor necrosis factor (TNF) family

Shater

Fawzy

Farid

et al. 2022

Lupus

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Objective Lupus nephritis (LN) is a significant consequence of systemic lupus erythematosus (SLE). To the best of our knowledge, this is the first work that focuses on evaluation of serum interleukin (IL-) 21 as a diagnostic biomarker of LN activity, compared to B lymphocyte stimulator (BlyS), tumor necrosis factor ligand superfamily member 13 (TNF-SF13), and traditional techniques of active LN attempting to compare their diagnostic usefulness. Methods Serum levels of IL-21, BlyS, and TNF-SF13 during LN were investigated. Twenty-five biopsy-proven, active LN female patients and 15 SLE patients without active LN and 20 healthy controls (HCs) joined this work. Results Serum IL-21 level was significantly higher in active LN group than in inactive LN group. Correlation analysis showed that serum IL-21 levels were significantly correlated with total SLEDAI (r = 0.41, p = 0.03), renal-SLEDAI (r = 0.48, p = 0.04), renal activity index (AI) (r = 0.93; p < 0.001), and 24-h proteinuria (r = 0.51; p > 0.008). Receiver operating characteristic curve (ROC) revealed the ability of serum IL-21 to discriminate between active and inactive LN with 70% sensitivity at >240 pg/ml cutoff point (AUC 0.809). Conclusion For Egyptian SLE patients, serum levels of IL-21 were superior to TNF-SF13 and BlyS and correlated significantly with the activity indexes of LN, indicating a promising role as a potential biomarker of active LN.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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The potential use of serum interleukin-21 as biomarker for lupus nephritis activity compared to cytokines of the tumor necrosis factor (TNF) family

Shater

Fawzy

Farid

et al. 2022

Lupus

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“…Despite the normal functions, IL-4 and IL-21 are highly involved in the progression of autoimmune diseases. The genetic associations between IL-4/IL-21 and autoimmune diseases had been well documented (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). Furthermore, elevated IL-4/IL-21 serum levels and increased numbers of IL-4/IL-21 producing T cells were observed in several human autoimmune conditions (34)(35)(36)(37)(38)(39)(40)(41)(42).…”

Section: Introductionmentioning

confidence: 99%

Interleukins 4 and 21 Protect Anti-IgM Induced Cell Death in Ramos B Cells: Implication for Autoimmune Diseases

Hui¹,

Wu²,

Leung³

2022

Front. Immunol.

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Interleukins 4 (IL-4) and 21 (IL-21) belong to the common gamma chain cytokine family which are highly involved in the progression of autoimmune diseases. While IL-4 is well known to be involved in the suppression of apoptosis of autoreactive B cells, the role played by IL-21 remains unclear. In the current study, we activated the human Burkitt’s lymphoma Ramos B cells with anti-IgM to mimic B cell hyperactivation observed in patients of autoimmune diseases. Consistent with other reported findings, anti-IgM led to the downregulation of proteins involved in B cell survival and proliferation, as well as the activation of caspase 3 activity and DNA damage, resulting in apoptotic cell death after 48-hour treatment. Although both IL-4 and IL-21 reversed anti-IgM-induced apoptosis and cell cycle arrest, they did so via different mechanisms: while IL-4 could directly suppress anti-IgM-induced caspase 3 activation and marker indicative of DNA damage, IL-21 could induce B cell proliferation in the presence of anti-IgM. Importantly, IL-21 also suppressed activation induced cell death in human primary B cells. Pre-treatment with clinically validated JAK inhibitors completely reversed the effects of IL-4 and IL-21 to rescue anti-IgM induced cell death and DNA damage. The results indicate the underlying mechanisms of how IL-4 and IL-21 differentially promote survival of hyperactivated B cells and provide hints to treat autoimmune diseases.

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“…SLE disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). There were twenty-four symptoms linked to lupus discovered, and each one was given a weighted score (Ahmed et al, 2017).…”

Section: Study Populationmentioning

confidence: 99%

Association between IL-23R rs11209026 Gene polymorphism and soluble interleukin 23 receptor (△9) in Iraqi patients with and without lupus nephritis

Allawe

Abdullah

Abed

2022

ijhs

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Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by the uncontrolled formation of antibodies, overproduction of pro-inflammatory cytokines with a genetic background that is poorly understood. This case-control study comprised 80 SLE patients, SLE patients who met the American College of Rheumatology (ACR) criteria (40 SLE and 40 LN groups), and 40 healthy controls. All participants' serum IL-23R levels were determined using an enzyme-linked immunosorbent assay (ELISA). 40 patients (20 SLE and 20 LN groups) and 12 age- and sex-matched healthy controls were genotyped for IL-23R gene polymorphisms (rs11209026 G>A) by direct DNA sequencing. As for sIL-23R levels, the results showed non-significant differences between the groups of the patients (0.18(0.11-7.50) vs 0.17(0.12- 3.73) (P= 0.751) in SLE and LN, respectively) and the control group (0.17 (0.12-2.69) (P=0.713) vs (P=0.934) in SLE and LN, respectively). Analysis of the rs11209026 sequencing results showed that most patients and the control group share the same genotype, which is GG, and that the A allele is underrepresented in the studied groups, as the AA genotype did not appear in the results. Our results suggest that rs11209026 affects the production of the soluble form of IL-23R.

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The association of single nucleotide polymorphism of interleukin-21 gene and serum interleukin-21 levels with systemic lupus erythematosus

Cited by 6 publications

References 29 publications

The potential use of serum interleukin-21 as biomarker for lupus nephritis activity compared to cytokines of the tumor necrosis factor (TNF) family

The potential use of serum interleukin-21 as biomarker for lupus nephritis activity compared to cytokines of the tumor necrosis factor (TNF) family

Interleukins 4 and 21 Protect Anti-IgM Induced Cell Death in Ramos B Cells: Implication for Autoimmune Diseases

Association between IL-23R rs11209026 Gene polymorphism and soluble interleukin 23 receptor (△9) in Iraqi patients with and without lupus nephritis

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