Serum interleukin-18 levels in patients with systemic lupus erythematosus: Relation with disease activity and lupus nephritis

Mohsen, Mona; Karim, S.A. Abdel; Abbas, Tarek M.; Amin, Maha M

doi:10.1016/j.ejr.2012.09.005

Cited by 18 publications

(14 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Elevated levels of IL-18 in SLE patients have been reported in several late studies particularly in patients with clinically active systemic illness [34][35][36][37]. Results of the current study are in agreement with those obtained by Esfandiari et al [33], Wong et al [37], as well as Amerio et al [38], where the researchers illustrated a significant elevation in IL-18 concentration in patients with SLE compared with controls (P < 0.001), which correlated with the SLEDAI activity score in their patients population [39]. In contrast to these studies, Robak et al [7] did not find significant differences in the levels of IL-18 between active and inactive SLE in their work, which might have been explained by the fact that SLE is a heterogeneous disease in which variability in the mean levels of certain cytokines is expected with different phases of disease activity as well as with therapeutic interventions.…”

Section: Discussionsupporting

confidence: 93%

Serum interleukin-18 and interleukin-10 levels in systemic lupus erythematosus: correlation with SLEDAI score and disease activity parameters

El-Fetouh

Mohammed

Abozaid

2014

Egypt Rheumatol Rehabil

View full text Add to dashboard Cite

AimThe aim of the study was to assess serum levels of interleukin (IL)-18 and IL-10 in systemic lupus erythematosus (SLE) patients and their relationship with disease activity. Patients and methodsThirty patients with SLE and 20 healthy controls were investigated in this study. The serum IL-18 and IL-10 levels were determined using enzyme-linked immunosorbent assay and their correlations with the disease activity were measured using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and laboratory parameters, including erythrocyte sedimentation rate, anti-ds DNA antibody, complement 3, and complement 4 levels were analyzed. ResultsThe serum IL-18 and serum IL-10 levels were significantly higher (mean values 1770.2 ± 360.4 and 842.65 ± 315.37 pg/ml for IL-18 and IL-10, respectively) in SLE patients compared with the controls (110.65 ± 30.37 vs. 76 ± 14.2 pg/ml, respectively, P < 0.001). The increase in serum levels of IL-18 and IL-10 directly and significantly correlated with each other (r = 0.404, P = 0.037). Furthermore, such an increase in the levels of these two cytokines showed a highly significant positive correlation with the SLEDAI scores and anti-ds DNA in the studied patients (P < 0.001). ConclusionThe circulating IL-18 and IL-10 concentrations were significantly elevated in SLE patients and correlated with the SLEDAI score. The study emphasized that there exists an upregulated proinflammatory as well as anti-inflammatory responses in patients with active SLE; however, the anti-inflammatory response is not enough to suppress the active disease. Identifying the exact contribution of the currently studied cytokines might provide future insights for targeted therapeutic strategies in SLE.[Downloaded free from http://www.err.eg.net on Sunday, June 07, 2015, IP: 49.204.26.195] Serum IL-18 and IL-10 in

show abstract

Section: Discussionsupporting

confidence: 93%

Serum interleukin-18 and interleukin-10 levels in systemic lupus erythematosus: correlation with SLEDAI score and disease activity parameters

El-Fetouh

Mohammed

Abozaid

2014

Egypt Rheumatol Rehabil

View full text Add to dashboard Cite

show abstract

“…This mesangial autocrine growth factor was shown to play a pivotal role in mesangial cell proliferation, which is essential for the progression of various glomerular diseases [ 74 ]. Our study did not confirm IL18 as a useful biomarker to assess the activity of renal disease, as reported by others [ 42 , 43 ]. On the other hand, our results nominated spectrum of novel biomarkers of renal involvement for further confirmation studies.…”

Section: Discussioncontrasting

confidence: 68%

“…Further highly upregulated proteins, IL18 and sulfotransferase 1A1, were already reported in autoimmunity. An elevated IL18 serum level was reported in SLE [ 42 ], especially in LN patients [ 43 , 44 ]. Regarding sulfotransferase 1A1, higher activity was found in autoimmune thyroid disease glands compared to normal thyroids [ 45 ], but no information yet exists in SLE.…”

Section: Discussionmentioning

confidence: 99%

Serum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by PEA immunoassay

et al. 2017

View full text Add to dashboard Cite

BackgroundSystemic lupus erythematosus (SLE) is a remarkably heterogeneous autoimmune disease. Despite tremendous efforts, our knowledge of serum protein patterns in severe SLE phenotypes is still limited. We investigated the serum protein pattern of SLE, with special emphasis on irreversible organ damage and active lupus nephritis (LN) as assessed by renal Systemic Lupus Erythematosus Disease Activity Index.MethodsWe used proximity extension immunoassay (PEA, Proseek Multiplex, Olink) to assess the serum levels of ninety-two inflammation-related proteins in Czech patients with SLE (n = 75) and age-matched healthy control subjects (n = 23). Subgroup analysis was carried out on the basis of organ damage (with/without, 42/33) and biopsy-proven LN (with/without, 27/48; active LN, n = 13; inactive LN, n = 14).ResultsOf thirty deregulated proteins between SLE and the healthy controls (P corr < 0.05), the top upregulated proteins in SLE were sirtuin 2, interleukin 18 (IL18), and caspase 8 (P corr < 0.0006). Of these, sirtuin 2 and caspase 8 had not yet been reported with SLE. Elevated levels of IL8, CCL2/MCP1, CCL11, and MMP10 (P corr < 0.05) were detected in patients with organ damage for which the serum levels of CCL11 and MMP10 were particularly informative in organ damage prediction. Comparing patients based on LN, elevated levels of CSF1, sIL15RA, sCD40, sCX3CL1, caspase 8, sIL18R1, bNGF, and GDNF (P corr < 0.05) were detected in active LN. Except GDNF, all LN-associated markers showed usefulness in prediction of active renal disease.ConclusionsThis highly sensitive PEA analysis identified the serum pattern of SLE, organ damage, and active LN, with many novel candidate proteins detected. Their exact role and suitability as biomarkers in SLE deserve further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-017-9167-8) contains supplementary material, which is available to authorized users.

show abstract

“…Expression of XCL1 (X-C Motif Chemokine Ligand 1) by crosspresenting CD8 + dendritic cells has been reported to determine cooperation with CD8+ T cells in murine models 48 . IL18 is a pro-inflammatory cytokine that plays an important role in generating inflammation in lupus nephritis 49 . PRDX2 (Peroxiredoxin 2) is an antioxidant that plays a key role in inflammation 50 .…”

Section: Cell-specific Transcriptional Differences Between Two Molecumentioning

confidence: 99%

Integrative transcriptomic analysis of SLE reveals IFN-driven cross-talk between immune cells

Panwar

Schmiedel

Liang

et al. 2020

Preprint

View full text Add to dashboard Cite

The systemic lupus erythematosus (SLE) is an incurable autoimmune disease disproportionately affecting women and may lead to damage in multiple different organs. The marked heterogeneity in its clinical manifestations is a major obstacle in finding targeted treatments and involvement of multiple immune cell types further increases this complexity. Thus, identifying molecular subtypes that best correlate with disease heterogeneity and severity as well as deducing molecular cross-talk among major immune cell types that lead to disease progression are critical steps in the development of more informed therapies for SLE. Here we profile and analyze gene expression of six major circulating immune cell types from patients with well-characterized SLE (classical monocytes (n=64), T cells (n=24), neutrophils (n=24), B cells (n=20), conventional (n=20) and plasmacytoid (n=22) dendritic cells) and from healthy control subjects. Our results show that the interferon (IFN) response signature was the major molecular feature that classified SLE patients into two distinct groups: IFN-signature negative (IFNneg) and positive (IFNpos). We show that the gene expression signature of IFN response was consistent (i) across all immune cell types, (ii) all single cells profiled from three IFNpos donors using single-cell RNA-seq, and (iii) longitudinal samples of the same patient. For a better understanding of molecular differences of IFNpos versus IFNneg patients, we combined differential gene expression analysis with differential Weighted Gene Co-expression Network Analysis (WGCNA), which revealed a relatively small list of genes from classical monocytes including two known immune modulators, one the target of an approved therapeutic for SLE (TNFSF13B/BAFF: belimumab) and one itself a therapeutic for Rheumatoid Arthritis (IL1RN: anakinra). For a more integrative understanding of the cross-talk among different cell types and to identify potentially novel gene or pathway connections, we also developed a novel gene coexpression analysis method for joint analysis of multiple cell types named integrated WGNCA (iWGCNA). This method revealed an interesting cross-talk between T and B cells highlighted by a significant enrichment in the expression of known markers of T follicular helper cells (Tfh), which also correlate with disease severity in the context of IFNpos patients. Interestingly, higher expression of BAFF from all myeloid cells also shows a strong correlation with enrichment in the expression of genes in T cells that may mark circulating Tfh cells or related memory cell populations. These cell types have been shown to promote B cell class-switching and antibody production, which are well-characterized in SLE patients. In summary, we generated a large-scale gene expression dataset from sorted immune cell populations and present a novel computational approach to analyze such data in an integrative fashion in the context of an autoimmune disease. Our results reveal the power of a hypothesis-free and datadriven approach to discover drug t...

show abstract

Serum interleukin-18 levels in patients with systemic lupus erythematosus: Relation with disease activity and lupus nephritis

Cited by 18 publications

References 26 publications

Serum interleukin-18 and interleukin-10 levels in systemic lupus erythematosus: correlation with SLEDAI score and disease activity parameters

Serum interleukin-18 and interleukin-10 levels in systemic lupus erythematosus: correlation with SLEDAI score and disease activity parameters

Serum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by PEA immunoassay

Integrative transcriptomic analysis of SLE reveals IFN-driven cross-talk between immune cells

Contact Info

Product

Resources

About