Plasma cytokines as potential biomarkers of kidney damage in patients with systemic lupus erythematosus

Abstract

Background Systemic lupus erythematosus is a heterogeneous chronic inflammatory autoimmune disorder characterized by an exacerbated expression of cytokines and chemokines in different tissues and organs. Renal involvement is a significant contributor to the morbidity and mortality of systemic lupus erythematosus, and its diagnosis is based on renal biopsy, an invasive procedure with a high risk of complications. Therefore, the development of alternative, non-invasive diagnostic tests for kidney disease in patients with systemic lupus erythematosus is a priority. Aim To evaluate the plasma levels of a panel of cytokines and chemokines using multiplex xMAP technology in a cohort of Colombian patients with active and inactive systemic lupus erythematosus, and to evaluate their potential as biomarkers of renal involvement. Results Plasma from 40 systemic lupus erythematosus non-nephritis patients and 80 lupus nephritis patients with different levels of renal involvement were analyzed for 39 cytokines using Luminex xMAP technology. Lupus nephritis patients had significantly increased plasma eotaxin, TNF-α, interleukin-17-α, interleukin-10, and interleukin-15 as compared to the systemic lupus erythematosus non-nephritis group. Macrophage-derived chemokine, growth regulated oncogene alpha, and epidermal growth factor were significantly elevated in systemic lupus erythematosus non-nephritis patients when compared to lupus nephritis individuals. Plasma eotaxin levels allowed a discrimination between systemic lupus erythematosus non-nephritis and lupus nephritis patients, for which we performed a receiver operating characteristic curve to confirm. We observed a correlation of eotaxin levels with active nephritis (Systemic Lupus Erythematosus Disease Activity Index). Our data indicate that circulating cytokines and chemokines could be considered good predictors of renal involvement in individuals with systemic lupus erythematosus.

Inhibition of EZH2 Ameliorates Lupus‐Like Disease in MRL/lpr Mice

“…We observed reduced concentrations of TNF, IFNγ, CCL2, RANTES/CCL5, IL‐10, IL‐12, IL‐12p40, and MIP‐1β/CCL4 in the plasma from mice in the DZNep‐treated groups compared to controls. All of these cytokines and chemokines have been reported to be elevated in lupus patients . Chemokines such as RANTES/CCL5, monocyte chemotactic protein 1/CCL2, and MIP‐1β/CCL4 contribute to lupus pathogenesis by recruiting leukocytes and other effector cells to inflamed tissues, causing damage .…”

“…Chemokines such as RANTES/CCL5, monocyte chemotactic protein 1/CCL2, and MIP‐1β/CCL4 contribute to lupus pathogenesis by recruiting leukocytes and other effector cells to inflamed tissues, causing damage . IL‐10 and TNF have been shown to be up‐regulated in lupus patients experiencing renal involvement, and their levels correlate with disease activity . IFNγ has been found to contribute to the development of lupus through promotion of autophagy in lupus T cells, and potentially the persistence of pathogenic T cell subsets .…”

Inhibition of EZH2 ameliorates lupus-like disease inMRL/lprmice

“…We observed reduced concentrations of TNF, IFN-γ, CCL2, RANTES/CCL5, IL-10, IL-12, IL-12p40, and MIP-1β/CCL4 in the plasma of the DZNep-treated groups compared to controls. All of these cytokines and chemokines have been reported to be elevated in lupus patients (17)(18)(19)(20)(21). Chemokines such as RANTES/CCL5, MCP-1/CCL2, and MIP-1β/CCL4 contribute to lupus pathogenesis by recruiting leukocytes and other effector cells to inflamed tissues, causing damage (17)(18)(19).…”

“…Chemokines such as RANTES/CCL5, MCP-1/CCL2, and MIP-1β/CCL4 contribute to lupus pathogenesis by recruiting leukocytes and other effector cells to inflamed tissues, causing damage (17)(18)(19). IL-10 and TNF have been reported to be upregulated and correlated with disease activity in lupus patients experiencing renal involvement (17,20). IFN-γ has been shown to contribute to the development of lupus through promotion of autophagy in lupus T cells, and potentially the persistence of pathogenic T cell subsets (20).…”

“…IL-10 and TNF have been reported to be upregulated and correlated with disease activity in lupus patients experiencing renal involvement (17,20). IFN-γ has been shown to contribute to the development of lupus through promotion of autophagy in lupus T cells, and potentially the persistence of pathogenic T cell subsets (20). Dysregulation of IL-12 has been reported in patients with lupus (22), and a recent clinical trial adding ustekinumab, which targets IL-12p40, to standard-of-care in lupus patients in a phase II trial showed promising results (23).…”