Urinary monocyte chemoattractant protein-1 as a biomarker of lupus nephritis activity in children

Abstract

Systemic lupus erythematosus (SLE) is a life-long, life-limiting and multi-systemic autoimmune disease. Glomerulonephritis is one of the most serious manifestations of SLE. Younger children have an increased incidence, severity and morbidity of lupus nephritis (LN) compared with adult-onset disease. Monocyte chemoattractant protein-1 (MCP-1) enhances leukocyte adhesiveness and endothelial permeability in the kidneys of murine and human LN models. Our study aimed to assess the role of urinary MCP-1 in the early diagnosis of LN activity. Sixty children, of whom 45 children aged from six to 12 years old and of both sexes (15 SLE patients without nephritis, 15 active LN and 15 inactive LN) fulfilling the American College of Rheumatology Classification Criteria for SLE were studied in comparison with 15 healthy subjects. We investigated the serum and urinary MCP-1 in all groups using the enzyme-linked immunosorbent assay test. Urinary MCP-1 was significantly higher in active LN in comparison with inactive LN and controls, and also significantly higher in inactive LN in comparison with SLE without nephritis and controls. There was also a significant difference between SLE without nephritis and controls. Serum MCP-1 was significantly higher in the group with active LN in comparison with the inactive group and SLE without nephritis and controls, but there was no significant difference between SLE and controls. The urinary MCP-1 level correlated well with SLE disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Urinary MCP-1 correlates positively with proteinuria, blood urea nitrogen level and creatinine and negatively with hemoglobin and creatinine clearance. We concluded that measurement of MCP-1 in urine may be useful for monitoring the severity of renal involvement in SLE. We recommend measuring urinary MCP-1 in pediatric SLE for the early diagnosis of LN and for the evaluation of the severity of renal involvement.

A functional SNP MCP-1 (−2518A/G) predispose to renal disorder in Indian Systemic Lupus Erythematosus patients

“…Albeit a strong relationship between urine MCP-1 (uMCP-1) levels and disease severity has been widely reported [21,22], serum MCP-1 (sMCP-1) have also been documented to be associated with active LN in SLE patients [23]. MCP-1 accounts monocytes/macrophages infiltration and causes renal injury [24].…”

Urinary biomarkers in lupus nephritis

“…MCP-1 belongs to the CC-chemokine family, is encoded on chromosome 17, and is composed of 76 ​amino acids [ 75 ]. In the kidney, it is produced by mesangial, tubular, epithelial cells, and in smooth muscle [ 76 ]. It is mainly expressed by monocytes, activated macrophages, T cells, and NK cells [ 74 ].…”

Emerging biomarkers of chronic kidney disease in children

“…Additionally, patients with glomerular disease had higher MCP-1 as compared with non-glomerular disease patients [64]. Urinary MCP-1 was identified as a marker of kidney disease severity in children with SLE [65]. In animal models of lupus nephritis, MCP-1 antagonists have limited kidney disease progression, suggesting MCP-1 has a primary role in disease activity [66].…”