The association of cytokines with disease activity and damage scores in systemic lupus erythematosus patients

McCarthy, Eoghan; Smith, Siobhan; Lee, Ruth Z.; Cunnane, Gaye; Doran, Michele F.; Donnelly, Suzanne; Howard, Donough; O’Connell, Paul; Kearns, Grainne; Gabhann, Joan Ní; Jefferies, Caroline A.

doi:10.1093/rheumatology/ket428

Cited by 77 publications

(72 citation statements)

References 31 publications

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“…Li et al . indicated that linc0597 and linc0949 not only involved in innate immunity but also regulate the induction of proinflammatory cytokines like tumor necrosis factor (TNF)-α and interleukin (IL)-6 [35], both of which are implicated in SLE pathogenesis [36–39]. However, linc0949, which is present at low levels in PBMCs of patients with SLE, shows no significant difference between total SLE patients and healthy controls in our study.…”

Section: Discussionmentioning

confidence: 50%

Identification of long non-coding RNAs GAS5, linc0597 and lnc-DC in plasma as novel biomarkers for systemic lupus erythematosus

Leng

et al. 2017

Oncotarget

103

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Despite increasing evidence that long non-coding RNAs (lncRNAs) widely take part in human diseases, the role of lncRNAs in systemic lupus erythematosus (SLE) is largely unknown. In this study, we performed a two-stage study to explore the plasma levels of five lncRNAs (GAS5, linc0949, linc0597, HOTAIRM1 and lnc-DC) and their potential as SLE biomarkers. Compared with healthy controls, plasma levels of GAS5 and lnc-DC were significantly decreased (P < 0.001 and P = 0.002, respectively) while linc0597 were overexpressed in SLE patients (P < 0.001). When SLE patients were divided into SLE without nephritis and lupus nephritis (LN), the levels of lnc-DC were significantly higher in LN compared with SLE without nephritis (P = 0.018), but no significant difference in levels of GAS5 and linc0597 were found between LN and SLE without nephritis; plasma linc0949 level showed no significant difference in all comparisons. Further evaluation on potential biomarkers showed that GAS5, linc0597 and lnc-DC may specifically identify patients with SLE, the combination of GAS5 and linc0597 provided better diagnostic accuracy; lnc-DC may discriminate LN from SLE without nephritis. In summary, GAS5, linc0597 and lnc-DC in plasma could be potential biomarkers for SLE.

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Section: Discussionmentioning

confidence: 50%

Identification of long non-coding RNAs GAS5, linc0597 and lnc-DC in plasma as novel biomarkers for systemic lupus erythematosus

Leng

et al. 2017

Oncotarget

103

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“…The induction of these pro-inflammatory mediators is facilitated through the binding of high-mobility group box 1 protein, engagement of Toll-like receptor 2 (TLR-2) and receptor for advanced glycation end-products (RAGE), activation of the MAPK, protein kinase C (PKC), inhibitor of kappa-light chain-enhancer of activated B cells (IκB) and nuclear factor kappa B (NF-κB) signaling pathways, and endoplasmic reticulum stress 20, 32– 35 . Correlation between serum levels of IL-1β, IL-6, TNF-α, hyaluronan, and lipocalin and disease activity in patients with SLE further highlights the importance of these inflammatory markers in the pathogenesis of LN 17, 36– 39 .…”

Section: Recent Knowledge On Renal Inflammation In Lupus Nephritismentioning

confidence: 91%

Recent advances in the understanding of renal inflammation and fibrosis in lupus nephritis

2017

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Lupus nephritis is a potentially reversible cause of severe acute kidney injury and is an important cause of end-stage renal failure in Asians and patients of African or Hispanic descent. It is characterized by aberrant exaggerated innate and adaptive immune responses, autoantibody production and their deposition in the kidney parenchyma, triggering complement activation, activation and proliferation of resident renal cells, and expression of pro-inflammatory and chemotactic molecules leading to the influx of inflammatory cells, all of which culminate in destruction of normal nephrons and their replacement by fibrous tissue. Anti-double-stranded DNA (anti-dsDNA) antibody level correlates with disease activity in most patients. There is evidence that apart from mediating pathogenic processes through the formation of immune complexes, pathogenic anti-dsDNA antibodies can bind to resident renal cells and induce downstream pro-apoptotic, pro-inflammatory, or pro-fibrotic processes or a combination of these. Recent data also highlight the critical role of macrophages in acute and chronic kidney injury. Though clinically effective, current treatments for lupus nephritis encompass non-specific immunosuppression and the anti-inflammatory action of high-dose corticosteroids. The clinical and histological impact of novel biologics targeting pro-inflammatory molecules remains to be investigated. Insight into the underlying mechanisms that induce inflammatory and fibrotic processes in the kidney of lupus nephritis could present opportunities for more specific novel treatment options to improve clinical outcomes while minimizing off-target untoward effects. This review discusses recent advances in the understanding of pathogenic mechanisms leading to inflammation and fibrosis of the kidney in lupus nephritis in the context of established standard-of-care and emerging therapies.

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“…These actions are initiated under the influence of IL-23, IL-17 and some other additional novel factors. The IL-23-IL-17 axis, rather than the loop of IL-12 and IFN-c, have a central role in the autoimmune inflammation, and interaction between IL-23 and IL-17 is not only essential for the onset phase, but also for the destruction phase of SLE characterized by the T cell-mediated activation of osteoclastogenesis [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…However, the role of single nucleotide polymorphisms (SNPs) in the genetic contribution to SLE still awaits extensive investigation. Moreover, the prevalence of SLE varies between ethnic groups and it is well established that patients from different genetic backgrounds have different disease severity and clinical phenotype [5]. Because, the IL-23/Th17 signaling pathway, consisting of IL-23/IL-23R and IL-17F encoding genes, might represents a candidate way for SLE pathogenesis with possible involvement in disease susceptibility, we decided to explore whether polymorphisms located in the IL-23A (703 G/A; rs11171806), IL-23R (rs1884444 G/T, rs10489629 G/A) and IL-17F (7488A/ G (His161Arg; rs763780) and 7383A / G (Glu126Gly; rs2397084)) genes are associated with SLE in a predominantly Polish population using case-control studies.…”

Section: Introductionmentioning

confidence: 99%

Impact of the IL-17F, IL-23 and IL-23R on susceptibility and phenotype of systemic lupus erythematosus

et al. 2016

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Systemic lupus erythematosus (SLE) is a disease characterized by excessive proinflammatory cytokine production and damage to multiple organ systems. To investigate the potential association between cytokine gene polymorphisms and SLE, we performed a case-control study based on Polish population. SLE patients and controls, were examined for IL-23A rs11171806 G/A and IL-23R (rs1884444 G/T, rs10489629 G/A) by TaqMan SNP genotyping assay, for IL-17F rs763780 A/G and rs2397084A/G using the PCR- RFLP method. An increased frequency of AG genotype as well as G allele of the IL-17F rs763780 was found in patients with SLE, as compared with healthy subjects (OR = 3.947; p = 0.001 and OR = 3.538; p = 0.002, respectively). Frequencies of the rs1884444 TT genotype (OR = 138.1) and the rs1884444 T allele (OR = 2.176) were also higher in SLE patients (both p < 0.0001). Overall, weak LD was observed between the IL-17F rs763780 A/G and rs2397084 A/G polymorphisms (D'-0.003, r - 0.000). From four possible haplotypes, frequencies of AG showed differences between both examined groups (p < 0.0001). We also observed a weak LD between the IL-23R rs10489629G/A and rs1884444 G/T (D'-0.199, r -0.026). The genotype-phenotype analysis showed significant association between the IL-17F rs2397084 and mean value of the hemoglobin (p = 0.01), the IL-17F rs763780 and age (p = 0.008) and lupus anticoagulant (p = 0.09), the IL-23 rs11171806 and urea (p = 0.08) and C3 complement (p = 0.03), and the IL-23R rs1884444 G/T and activated partial thromboplastin time (p = 0.06). Present findings indicated that IL-17F rs763780 A/G and IL-23R rs1884444 G/T polymorphisms may be involved in susceptibility to SLE in the Polish population.

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The association of cytokines with disease activity and damage scores in systemic lupus erythematosus patients

Abstract: Increased levels of a number of immunomodulatory cytokines relative to IL-12p70 in this Caucasian SLE patient population are seen in patients with renal involvement and are associated with increased accrual of damage at the 5-year follow-up.

Cited by 77 publications

References 31 publications

Identification of long non-coding RNAs GAS5, linc0597 and lnc-DC in plasma as novel biomarkers for systemic lupus erythematosus

Identification of long non-coding RNAs GAS5, linc0597 and lnc-DC in plasma as novel biomarkers for systemic lupus erythematosus

Recent advances in the understanding of renal inflammation and fibrosis in lupus nephritis

Impact of the IL-17F, IL-23 and IL-23R on susceptibility and phenotype of systemic lupus erythematosus

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