epidermal-growth-factor and Lupus-Erythematosus--Systemic

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease where the body's immune system targets cells and tissue in numerous organs, including the kidneys. Lupus nephritis (LN) is a highly heterogeneous disease, and diagnosis is difficult because clinical manifestations vary widely among patients. Comprehensive proteomic studies reported recently in LN have identified several urinary proteins which are also cell-surface receptors. If indeed these receptor proteins are also hyper-expressed within the kidneys, ligands to these receptors may be useful for drug targeting.. scRNA sequence data analysis and immunohistochemistry were performed on LN kidneys for expression of four implicated receptors, EGFR, FOL2R2, PDGF-RB, and TFRC.. In reported scRNA sequencing studies from 21 LN patients and 3 healthy control renal biopsies or renal-infiltrating immune cells from 24 LN biopsies, EGFR, FOLR2, PDGF-Rb, and TFRC were all hyper expressed within LN kidneys in comparison to healthy kidneys, either within resident renal cells or infiltrating leukocytes. Immunohistochemistry staining of murine lupus renal biopsies from lupus mice revealed EGFR, FOLR2, TFRC and PDGF-RB were elevated in LN kidneys. Immunohistochemistry staining of human Class II, Class III, and Class IV kidney tissue sections revealed EGFR, TFRC, and PDGF-RB were significantly elevated in proliferative LN kidneys.. These findings underscore the potential of EGFR, TFRC, FOLR2, and PDGF-RB as promising receptors for potential drug-targeting in LN.

Topics: Animals; Biomarkers; Epidermal Growth Factor; ErbB Receptors; Folate Receptor 2; Folic Acid; Humans; Kidney; Lupus Erythematosus, Systemic; Lupus Nephritis; Mice; Proteomics; Transferrin

There is a need for sensitive and specific biomarkers to predict kidney damage and therapeutic response in lupus nephritis (LN). Monocyte chemoattractant protein-1 (MCP-1) and epidermal growth factor (EGF) are cytokines with divergent roles. EGF or EGF/MCP1 ratio have been shown to correlate with prognosis in primary glomerulonephritis, but there is limited information in lupus nephritis (LN). This study evaluated the roles of MCP-1, EGF or their ratio as biomarkers of histopathology and response to treatment in LN.. This was a cross-sectional and observational study. Baseline urine MCP-1 and EGF levels in systemic lupus erythematosus (SLE) patients and controls (total n = 101) were compared, and levels were correlated with clinicopathological findings and subsequent response to treatment.. MCP-1 was higher in active LN (n = 69) compared to other SLE groups and controls, whereas EGF was not different. MCP-1 correlated with disease activity (proteinuria, renal SLEDAI, classes III/IV/V, and high activity index.) By contrast, EGF correlated with eGFR, but not with proteinuria, activity index, or class III/IV/V. MCP-1 was higher, and EGF was lower in high chronicity index. EGF/MCP-1 decreased with greater clinicopathological severity. In a subgroup with proliferative LN who completed six months of induction therapy (n = 41), EGF at baseline was lower in non-responders compared to responders, whereas MCP-1 was similar. By multivariable analysis, baseline EGF was independently associated with subsequent treatment response. Area under the curve for EGF to predict response was 0.80 (0.66-0.95). EGF ≥ 65.6 ng/ mgCr demonstrated 85% sensitivity and 71% specificity for response. EGF/MCP-1 did not improve the prediction for response compared to EGF alone.. MCP-1 increased with disease activity, whereas EGF decreased with low GFR and chronic damage. Urine EGF may be a promising biomarker to predict therapeutic response in LN. EGF/MCP-1 did not improve the prediction of response.

Topics: Biomarkers; Chemokine CCL2; Cross-Sectional Studies; Epidermal Growth Factor; Female; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Proteinuria