Glomerular accumulation of plasmacytoid dendritic cells in active lupus nephritis: Role of interleukin‐18

Tucci, Marco; Quatraro, Cosima; Lombardi, Lucia; Pellegrino, Cecilia; Dammacco, Franco; Silvestris, Franco

doi:10.1002/art.23186

Cited by 205 publications

(156 citation statements)

References 30 publications

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“…Our hypothesis may be supported by studies recently conducted by Tucci et al (2008), who reported increased production of IL-18 in patients with lupus nephritis [41]. Moreover, they found that patients with severe lupus nephritis exhibit a high accumulation of IL-18 within glomeruli [41].…”

Section: Discussionsupporting

confidence: 84%

“…Moreover, they found that patients with severe lupus nephritis exhibit a high accumulation of IL-18 within glomeruli [41]. They suggested that IL-18 is biosynthesized by macrophages within nephritic glomeruli, and this cytokine may chemoattract plasmacytoid dendritic cells to kidney glomeruli, leading to renal damage [41]. Wong et al (2002) also reported elevated production of IL-18 in SLE patients with renal disease [42].…”

Section: Discussionmentioning

confidence: 99%

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IL-18 105 A>C polymorphism contributes to renal manifestations in patients with SLE

et al. 2009

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SummarySystemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disorder characterized by various aberrations including increased production of IL-18.Since IL-18 105 A>C polymorphic variants have been linked to increased production of this cytokine, we investigated the prevalence of IL-18 105 A>C (rs549908) polymorphic variants in SLE patients (n=111) and controls (n=152).There were no significant differences in the distribution of IL-18 105 A>C polymorphic variants in SLE patients and controls. However, there was a significant association between the IL-18 105 AA genotype (recessive model) and renal manifestations OR=3.360 (1.523-7.415, P=0.0039) and the P value remained statistically significant after Bonferroni correction (P corr = 0.0351).Our findings indicate that the IL-18 105 AA genotype variant can contribute to renal manifestations in patients with SLE.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

IL-18 105 A>C polymorphism contributes to renal manifestations in patients with SLE

et al. 2009

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“…One explanation for the decreased SLAM expression on circulating pDCs in SLE could be that SLE IC-activated cells migrate from the circulation to inflamed tissues. Such redistribution from blood to tissues of pDCs that produce IFN-a was also described in SLE (42,43) and might explain our observation. On SLE NK cells, decreased expression of CD229 on CD56 dim NK cells and increased expression of CD319 and CD48 on CD56 bright NK cells were observed.…”

Section: Altered Expression Of Cd319 and Cd229 On Pdcs And Nk Cells Fsupporting

confidence: 85%

Systemic Lupus Erythematosus Immune Complexes Increase the Expression of SLAM Family Members CD319 (CRACC) and CD229 (LY-9) on Plasmacytoid Dendritic Cells and CD319 on CD56dim NK Cells

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Schlums

et al. 2013

The Journal of Immunology

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Patients with systemic lupus erythematosus (SLE) display an activated type I IFN system due to unceasing IFN-α release from plasmacytoid dendritic cells (pDCs) stimulated by nucleic acid–containing immune complexes (ICs). NK cells strongly promote the IFN-α production by pDCs; therefore, we investigated surface molecules that could be involved in the pDC–NK cell cross-talk. In human PBMCs stimulated with RNA-containing ICs (RNA-ICs), the expression of the signaling lymphocyte activation molecule (SLAM) family receptors CD319 and CD229 on pDCs and CD319 on CD56dim NK cells was selectively increased. Upregulation of CD319 and CD229 on RNA-IC–stimulated pDCs was induced by NK cells or cytokines (e.g., GM-CSF, IL-3). IFN-α–producing pDCs displayed a higher expression of SLAM molecules compared with IFN-α− pDCs. With regard to signaling downstream of SLAM receptors, pDCs expressed SHIP-1, SHP-1, SHP-2, and CSK but lacked SLAM-associated protein (SAP) and Ewing’s sarcoma-activated transcript 2 (EAT2), indicating that these receptors may act as inhibitory receptors on pDCs. Furthermore, pDCs from patients with SLE had decreased expression of CD319 on pDCs and CD229 on CD56dim NK cells, but RNA-IC stimulation increased CD319 and CD229 expression. In conclusion, this study reveals that the expression of the SLAM receptors CD319 and CD229 is regulated on pDCs and NK cells by lupus ICs and that the expression of these receptors is specifically altered in SLE. These results, together with the observed genetic association between the SLAM locus and SLE, suggest a role for CD319 and CD229 in the SLE disease process.

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“…The increased glomerular expression of IL-18 in established human LN was also reported by different groups. 7,16,33,41 To our knowledge, we are the first group to report expression of IL-18 in renal tissue of subclinical LN.…”

Section: Discussionmentioning

confidence: 94%

“…Moreover, a relationship between tubular IL-18 expression and renal disease activity has been demonstrated. 13,15 Tucci et al 16 in 2008 demonstrated decrease in peripheral plasmacytoid dendritic cells (DCs), which expressed IL-18 receptor, in patients with LN and they suggested that the high level of expression of IL-18 receptor by peripheral plasmacytoid DCs helps the DCs to relocate within glomeruli under IL-18 stimulation and promote renal damage. Furthermore, Hatef et al 17 in 2013 showed a correlation between IL-18 and serum Fas in patients with LN being highly significant in patients with severe SLE than those with milder disease.…”

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confidence: 99%

Interleukin-18 as a Biomarker of Subclinical Lupus Nephritis

et al. 2015

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Objectives:This study aims to investigate the relationship between serum interleukin-18 (IL-18) and its renal expression with histological classification of lupus nephritis in patients with insignificant proteinuria, and evaluate serum IL-18 as a biomarker of subclinical renal involvement in lupus patients. Patients and methods: Forty lupus patients (5 males, 35 females; mean age 26.3±7.9 years; range 16 to 52 years) with proteinuria less than 0.5 g/24 hours and 20 healthy controls (2 males, 18 females, mean age 25.5±6.3 years; range 16 to 49 years) were included. Patients underwent full history taking, thorough clinical examination, assessment of disease activity, measurement of serum IL-18, and renal biopsies for histopathological assessment and immunostaining for tissue expression of IL-18. Results: Lupus patients had significantly higher serum IL-18 levels than controls (612.4 and 209.3 pg/mL, respectively; p<0.01). Serum IL-18 was significantly higher in patients with classes III, IV and V lupus nephritis (609.1, 833.1 and 790 pg/mL, respectively) than in patients with class I and II (370 and 476.8 pg/mL, respectively). Immunostaining of IL-18 showed glomerular expression in classes IV and V, glomerular and tubular infiltration in class III, tubular pattern in class II and no staining in class I. Patients with diffuse glomerular IL-18 staining had higher levels of serum IL-18 than those with no staining (840.8 and 522.9 pg/mL, respectively; p=0.0). Those with diffuse tubular IL-18 staining had higher levels of serum IL-18 than those with no staining (514.2 and 393 pg/mL, respectively; p<0.05). Serum IL-18 correlated with serum creatinine and the activity index of renal biopsies. Conclusion: IL-18 may play a role in the pathogenesis of lupus nephritis. Results of this study showed that serum IL-18 reflects the extent of renal injury in lupus even in absence of significant proteinuria regardless of the level of disease activity; proposing its early role in pathogenesis of lupus nephritis. Thus serum IL-18 can be used as a biomarker that distinguishes the different histological classes of subclinical lupus nephritis.

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Glomerular accumulation of plasmacytoid dendritic cells in active lupus nephritis: Role of interleukin‐18

Cited by 205 publications

References 30 publications

IL-18 105 A>C polymorphism contributes to renal manifestations in patients with SLE

IL-18 105 A>C polymorphism contributes to renal manifestations in patients with SLE

Systemic Lupus Erythematosus Immune Complexes Increase the Expression of SLAM Family Members CD319 (CRACC) and CD229 (LY-9) on Plasmacytoid Dendritic Cells and CD319 on CD56dim NK Cells

Interleukin-18 as a Biomarker of Subclinical Lupus Nephritis

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