Interleukin-18 as a Biomarker of Subclinical Lupus Nephritis

Bakry, Samah Abdel Rahman El; Alhefny, Abdelazim; Al-Zifzaf, Dina S.; Nada, Ola; Kabarity, Rania H. El; Omar, Khaled

doi:10.5606/archrheumatol.2015.4675

Cited by 5 publications

(5 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among all the mediators that are significantly associated with HLA-DRB1 * 04 alelle, IFN-γ, IL-18, VEGF and LPO warrant further investigations as these immune mediators are robustly linked to the pathogenesis of LN in SLE patients ( Table 6 ). Some studies even suggested that IL-18 ( 95 , 97 , 98 ), IFN-γ ( 81 – 83 ), LPO ( 100 ) and VEGF ( 108 , 109 ) could serve as host biomarkers in assessing the renal disease activity and/or discerning between SLE patients with and without lupus nephritis.…”

Section: Discussionmentioning

confidence: 99%

HLA-DRB1*04 as a Risk Allele to Systemic Lupus Erythematosus and Lupus Nephritis in the Malay Population of Malaysia

et al. 2021

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease afflicting multiple organs. Lupus nephritis (LN) is a serious complication of SLE and remains a major cause of mortality and morbidity. Curative therapy remains unavailable as etiology from genetic and environmental factors is still unclear. The present study was conducted to elucidate the link between HLA-DRB1 gene polymorphisms with SLE and LN through clinical and laboratory/biological presentations in a population of Malaysian Malay females with SLE. A total of 100 Malay female SLE patients inclusive of 70 SLE patients without LN and 30 patients with LN were included in this study. HLA-DRB1 allele examination in SLE patients was performed using PCR-SSO, and the alleles' frequencies were compared with 951 publicly available datasets representing Malay healthy controls in Malaysia. Cytokines and free radical levels were detected by ELISA and bead-based multiplexed Luminex assays. The association between HLA-DRB1 alleles with clinical and serological manifestations and immune mediators was analyzed using different statistical approaches whenever applicable. Our study showed that HLA-DRB1*0405, HLA-DRB1*1502, and HLA-DRB1*1602 were associated with the increased risk of SLE while HLA-DRB1*1201 and HLADRB1*1202 alleles were associated with a lower risk of SLE development. Furthermore, HLA-DRB1*04 showed significant association to LN and arthritis while HLA-DRB1*15 was significantly associated with oral ulcer in Malay SLE patients. Association analysis of HLA-DRB1*04 with clinical and biological factors revealed that HLA-DRB1*04 was significantly associated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-nuclear antibody (ANA), C-reactive protein (CRP) in the blood, and total protein in the urine. SLE carriers with the HLA-DRB1*04 allele were significantly correlated to the increased levels of cytokines (IFN-y, GM-CSF, IL-17F, IL-18, IL-21, and VEGF) and were significantly showing negative correlation to IL-5 and free radicals (LPO and catalase enzyme) levels compared to SLE carriers without HLA-DRB1*04 allele. The results suggested that disease severity in SLE may be determined by HLA-DRB1 alleles. The risk of HLA-DRB1*04 allele with LN was supported by the demonstration of an intense inflammatory response in Malay SLE patients in Malaysia. More studies inclusive of a larger and multiple SLE cohorts in the future are warranted to validate these findings.

show abstract

Section: Discussionmentioning

confidence: 99%

HLA-DRB1*04 as a Risk Allele to Systemic Lupus Erythematosus and Lupus Nephritis in the Malay Population of Malaysia

et al. 2021

View full text Add to dashboard Cite

show abstract

“…9 In comparison with healthy controls, patients with lupus presented with significantly higher IL-18 levels in serum, which reflects the severity extent of renal damage in lupus. 10,11 Recent studies have demonstrated that lpr mice administered an IL-18 DNA vaccine exhibited a significant reduction in glomerulonephritis and renal damage, 12 suggesting that inhibition of IL-18 production may be an effective therapeutic strategy for LN.…”

Section: Introductionmentioning

confidence: 99%

Procyanidin B2 prevents lupus nephritis development in mice by inhibiting NLRP3 inflammasome activation

Sun

Tian

2018

Innate Immun

View full text Add to dashboard Cite

Lupus nephritis (LN) is a multifactorial event that contributes to the long-term mortality of systemic lupus erythematosus (SLE). Activation of NLRP3 inflammasome has been known to play a role in SLE pathogenesis. We evaluated the renal protection effects of procyanidin B2 (PCB2) and the involvement of NLRP3 in a mouse model involving MRL/lpr and MRL/MpJ mice. Kidney injury was evaluated by measuring the renal clinical and pathological features, renal immune complex deposition, and serum anti-double-stranded (anti-dsDNA) Abs. ELISA and Western blotting were used to detect NLRP3 inflammasome activation and IL-1β/IL-18 production. NLRP3 gene silencing was introduced into MRL/lpr mice by short hairpin RNA, and the renal damage was compared with the treatment of PCB2. PCB2 remarkably reduced renal damage in MRL/lpr mice, reflected by the reduced proteinuria, and serum levels of blood urea nitrogen and creatinine, as well as pathological features with less renal injury. PCB2 significantly reduced renal immune complex deposition and serum anti-dsDNA levels, notably inhibited the NLRP3 inflammasome activation, and reduced the renal and serum levels of IL-1β and IL-18 in MRL/lpr mice compared with those of NLRP3 gene-silenced MRL-lpr mice. PCB2 significantly suppressed LN in MRL-lpr mice by inhibiting the activation of NLRP3 inflammasome and subsequent IL-1β and IL-18 production. This finding explores a novel mechanism by which procyanidin exerts inflammatory suppression effects and its clinical benefits in LN prevention.

show abstract

“…In addition, several recent studies have reported correlations between IL-18 and disease severity, organ involvement and a list of classic testing biomarkers like anti-dsDNA antibody, C3, C4 and etc 32,37 . In lupus nephritis, IL-18 is also related with proteinuria and renal activity and elevates earlier than the occurrence of proteinuria and high disease severity score, indicating that IL-18 has the chance to be used as a predictive marker to distinguish diverse stages of LN, even in subclinical stage 41 . These updated findings can help broaden the clinical applications of IL-18 and enrich its comprehensive significance in SLE.…”

Section: Discussionmentioning

confidence: 99%

Correlation between circulating interleukin-18 level and systemic lupus erythematosus: a meta-analysis

Xiang

Yang

Wang

et al. 2021

Sci Rep

View full text Add to dashboard Cite

This study is a meta-analysis aimed at pooling reported data and clarifying the association between circulating level of interleukin-18 and systemic lupus erythematosus (SLE). We searched medical databases including Medline/Pubmed, Embase, Scopus, The Cochrane Library, and Web of Science thoroughly to obtain all related articles published before July 15th, 2020. We pooled computed standardized mean difference (SMD) and its 95% confidence interval using STATA 13.0 and exhibited in the form of forest graph. Meta-regression and subgroup analysis were also performed to explore the source of heterogeneity. Publication bias was first evaluated by the symmetry of the funnel plot and then Egger’s linear regression test. Thirty eligible studies from eighteen regions were finally included and the relevant data from these studies were pooled. The analysis results displayed that SLE patients showed a significantly higher level of circulating IL-18 level in comparison with healthy controls (SMD = 1.56, 95% CI [1.20–1.93]; I2 = 94.9%, p < 0.01). The conclusion was equally applicable in subgroups divided based on sample type, mean age, disease duration, and testing method. Patients with SLEDAI score higher than five, or who were Asian, White, Arab, or mixed ethnicity had an elevated level of IL-18, while the others didn’t. This meta-analysis has elucidated that compared with healthy people, the circulating level of IL-18 is considerably higher in SLE patients, which indicates the underlying role of IL-18 in SLE pathogenesis.

show abstract

Interleukin-18 as a Biomarker of Subclinical Lupus Nephritis

Cited by 5 publications

References 39 publications

HLA-DRB1*04 as a Risk Allele to Systemic Lupus Erythematosus and Lupus Nephritis in the Malay Population of Malaysia

HLA-DRB1*04 as a Risk Allele to Systemic Lupus Erythematosus and Lupus Nephritis in the Malay Population of Malaysia

Procyanidin B2 prevents lupus nephritis development in mice by inhibiting NLRP3 inflammasome activation

Correlation between circulating interleukin-18 level and systemic lupus erythematosus: a meta-analysis

Contact Info

Product

Resources

About