CD4+Foxp3+ T cells, interleukin-35 (IL-35) and IL-10 in systemic lupus erythematosus patients: Relation to disease activity

Bassiouny, M. Khalil; Sonbol, Ahmed; Eissa, Hend Abdelgader; El-Shanawany, Amira T.; Labeeb, Alaa

doi:10.1016/j.ejr.2018.08.001

Cited by 10 publications

(8 citation statements)

References 35 publications

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“…In this study, we showed that serum IL-35 levels were significantly higher in SLE patients than healthy controls. This finding is in agreement with previous studies which showed elevated levels of IL-35 in active SLE patients (17,18,43). However, no correlation was observed between serum IL-35 levels with SLEDAI-2K scores.…”

Section: Discussionsupporting

confidence: 92%

“…However, IL-35 also exerts pro-inflammatory effects by activating the production of IL-12 and IFN-g (15), and its expression is upregulated in autoimmune diseases such as rheumatoid arthritis (RA) where it augments the release of pro-inflammatory factors such as IL-1b and IL-6 (16). In SLE, multiple studies have reported that serum IL-35 levels are increased in established SLE patients on treatment (17,18).…”

Section: Introductionmentioning

confidence: 99%

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CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients

et al. 2021

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The receptors for IL-35, IL-12Rβ2 and gp130, have been implicated in the inflammatory pathophysiology of autoimmune diseases. In this study, we set out to investigate the serum IL-35 levels and the surface levels of IL-12Rβ2 and gp130 in CD3+CD4+, CD3+CD4─ and CD3─CD4─ lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients (n=50) versus healthy controls (n=50). The potential T cell subsets associated with gp130 transcript (i.e. IL6ST) expression in CD4+ T cells of SLE patients was also examined in publicly-available gene expression profiling (GEP) datasets. Here, we report that serum IL-35 levels were significantly higher in SLE patients than healthy controls (p=0.038) but it was not associated with SLEDAI-2K scores. The proportions of IL-12Rβ2+ and gp130+ cells in SLE patients did not differ significantly with those of healthy controls in all lymphocyte subpopulations investigated. Essentially, higher SLEDAI-2K scores were positively correlated with increased proportion of gp130+ cells, but not IL-12Rβ2+ cells, on CD3+CD4+ T cells (r=0.425, p=0.002, q=0.016). Gene Set Enrichment Analysis (GSEA) of a GEP dataset of CD4+ T cells isolated from SLE patients (n=8; GSE4588) showed that IL6ST expression was positively associated with genes upregulated in CD4+ T cells vs myeloid or B cells (q<0.001). In an independent GEP dataset of CD4+ T cells isolated from SLE patients (n=9; GSE1057), IL6ST expression was induced upon anti-CD3 stimulation, and that Treg, TCM and CCR7+ T cells gene sets were significantly enriched (q<0.05) by genes highly correlated with IL6ST expression (n=92 genes; r>0.75 with IL6ST expression) upon anti-CD3 stimulation in these SLE patients. In conclusion, gp130 signaling in CD3+CD4+ T cell subsets may contribute to increased disease activity in SLE patients, and it represents a promising therapeutic target for inhibition in the disease.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients

et al. 2021

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“…This result agreed with several studies. [27][28][29][30] This difference may be attributed to the heterogeneity of the disease, different patient populations and different sample sizes.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of autophagy‐related genes in Egyptian systemic lupus erythematosus patients

et al. 2020

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Disturbances in autophagy are known to be implicated in autoimmune disorders. Many studies have connected polymorphisms in autophagy‐related gene 5 (ATG‐5) to systemic lupus erythematosus (SLE). Our aim was the determination of the expression level of ATG‐5, Beclin‐1 and microtubule‐associated protein‐light chain 3 (LC‐3) in Egyptian SLE patients to investigate the impact of disturbances in autophagy genes on the incidence and progression of the disease. Also, we investigated the incidence of single nucleotide polymorphism (SNP) rs573775 in ATG‐5 gene among Egyptian SLE patients. Our results showed that the mean levels of Beclin‐1, LC‐3 and interleukin (IL)‐10 transcripts were significantly higher in SLE patients compared to healthy controls. The previous transcripts were positively correlated with SLE Disease Activity Index (SLEDAI). Beclin‐1 and LC‐3 transcripts were negatively correlated to complement component 3 (C3) levels. Only LC‐3 transcripts were negatively correlated to complement component 4 (C4). The rs573775 SNP of ATG‐5 with the variant allele was significantly associated with disease susceptibility, conferring a higher risk of SLE development. This variant allele was more prevalent in patients below 30 years, patients with anemia and in patients with anti‐double‐stranded DNA (dsDNA), confirming the essential role of ATG‐5 polymorphism in the susceptibility of Egyptian patients to SLE.

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“…[ 39 ] and Bassiouny et al . [ 40 ], who found that the levels of serum IL-35 were significantly higher in patients with SLE than in healthy controls. Similarly, IL-35 levels were reported to be significantly higher in SLE patients [ 41 , 42 ] which may imply the potential immunosuppressive and anti-inflammatory role of IL-35 in SLE.…”

Section: Discussionmentioning

confidence: 99%

“…[ 39 ] and Bassiouny et al . [ 40 ], who found that the levels of serum IL-35 were correlated with SLEDAI scores, and suggested that serum IL-35 levels are a highly sensitive and specific biomarker for detection of lupus activity.…”

Section: Discussionmentioning

confidence: 99%

Urine and serum interleukin 35 as potential biomarkers of lupus nephritis

Nassif¹

2021

cejoi

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Introduction Lupus nephritis (LN) is considered a serious manifestation of systemic lupus erythematosus (SLE). Therefore, a reliable non-invasive biomarker is a priority for monitoring renal involvement instead of the kidney biopsy. Interleukin 35 (IL-35) has an immunosuppressive and anti-inflammatory role in many autoimmune diseases. However, its role in LN still needs to be elucidated. Aim of the study To evaluate urine and serum levels of IL-35 in SLE patients with LN and without nephritis identifying their potential as biomarkers of renal involvement. Material and methods Urine and serum levels of IL-35 were measured in 42 SLE patients, divided into 22 with LN and 20 without LN, and 20 matched healthy controls using enzyme-linked immunosorbent assay (ELISA). SLE disease activity was assessed for patients by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Results Levels of serum and urine IL-35 were significantly higher (p < 0.001) in the LN group compared with those without LN and with controls. In LN patients, a strong correlation (p < 0.001) was observed between serum and urine IL-35 levels with SLEDAI-2K score (r = 0.677 and 0.806 respectively). Furthermore, proteinuria had a strong and significant correlation (p ˂ 0.001) with serum and urinary IL-35 levels in the patients with LN. Serum IL-35 had 90.9% sensitivity and 85% specificity while urine IL-35 had 95.5% sensitivity and 75% specificity to differentiate LN from healthy individuals. Conclusions Urine and serum IL-35 may aid in assessment of renal involvement in SLE patients, serving as potential biomarkers of LN.

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CD4+Foxp3+ T cells, interleukin-35 (IL-35) and IL-10 in systemic lupus erythematosus patients: Relation to disease activity

Cited by 10 publications

References 35 publications

CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients

CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients

Evaluation of autophagy‐related genes in Egyptian systemic lupus erythematosus patients

Urine and serum interleukin 35 as potential biomarkers of lupus nephritis

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