Urinary Soluble Alpha Chain of the Interleukin-2 Receptor as a Biomarker of Active Lupus Nephritis in Egyptian Children With Juvenile Systemic Lupus Erythematosus

Abstract

Objectives This study aims to assess the urinary soluble alpha chain of the interleukin-2 receptor (sCD25) concentrations in patients with juvenile systemic lupus erythematosus (JSLE) and to evaluate its validity to be a possible marker of disease activity in patients with lupus nephritis (LN). Patients and methods We assessed sCD25 concentrations in urine samples obtained from 53 JSLE patients (15 males, 38 females; median age 11 years; range, 7 to 17 years) and 30 age- and sex-matched apparently healthy controls (10 males, 20 females; median age 10 years; range, 6 to 16 years). Concentrations were normalized according to urinary creatinine excretion. JSLE patients were subjected to clinical examination and assessment of overall disease activity by Systemic Lupus Erythematous Disease Activity Index (SLEDAI), while evaluation of LN activity was preformed using Systemic Lupus International Collaborating Clinics (SLICC) renal activity score. Results The JSLE patients had significantly higher normalized urinary sCD25 concentrations compared to the healthy controls (p=0.001). Patients with active LN had significantly higher normalized urinary sCD25 levels than active JSLE patients without LN (p=0.002) and JSLE patients with inactive disease (p<0.001). A significant positive correlation was found between normalized urinary sCD25 concentrations with different activity parameters such as proteinuria (p=0.004), SLEDAI (p<0.001), renal SLEDAI (p<0.001), and SLICC renal activity score (p<0.001). A significant negative correlation was found between urinary sCD25 and complement 3 (p<0.001). Conclusion Urinary concentrations of sCD25 were significantly elevated in JSLE patients, particularly in those with active LN. The remarkable association between urinary sCD25 concentrations and different renal disease activity parameters implies that urinary sCD25 can be a beneficial marker to monitor active nephritis in JSLE patients.

The soluble IL‐2 receptor α/CD25 as a modulator of IL‐2 function

“…Of note, the usefulness of sIL-2Rα concentration to assess disease severity is not limited to blood, as sIL-2Rα can also be found in other body fluids. Examples are urinary sIL-2Rα concentration, which can be exploited to assess nephritis severity in patients with (juvenile) systemic lupus erythematosus [77,78], or the CSF sIL-2Rα amount, which is an indicator for central nervous system involvement in patients with haemophagocytic lymphohistiocytosis [79]. In addition to disease severity, response to therapy can also be estimated from sIL-2Rα levels.…”

Current views on lupus in children

“…Renal BILAG defined [104,112--114] Renal SLEDAI defined [106,107,115--118] AGP-1 Urine Renal BILAG defined [102--104,111,113,114] Renal SLEDAI defined [106,114] CP Urine Renal BILAG defined [102--104,113,114] Renal SLEDAI defined [114] LPGDS Urine Renal BILAG defined [103,104,114] Renal SLEDAI defined [106,113,114] Transferrin Urine Renal BILAG defined [104,114,103] Renal SLEDAI defined [114,106,113] VCAM-1 Urine Renal BILAG defined [103,104] S100 A4 Urine Renal SLEDAI defined [109] S100 A6 Urine Renal SLEDAI defined [109] S100 A8/A9 Urine Renal SLEDAI defined [109] S100 A12 Urine Renal BILAG defined [119] Renal SLEDAI defined [109] S100 A8/A9 Serum Renal BILAG defined [119] sCD25 Urine Renal SLEDAI defined [120] sCD25 Serum Renal SLEDAI defined [120] AGP-1, CP, LPGDS, Transferrin Urine Optimal panel for active LN identification (renal BILAG defined) in UK, US [104], and SA cohorts [103] LPGDS, CP, transferrin, MCP- Predictors of response to therapy…”

Biomarkers Associated with Organ-Specific Involvement in Juvenile Systemic Lupus Erythematosus

“…The soluble alpha chain of the interleukin-2 receptor (also called soluble CD25—sCD25) is produced by the proteolytic cleavage of interleukin 2 receptor (IL-2R) subunit alpha from cell membrane, following T cell activation. sCD25 has been found to be a suitable serum and urine biomarker for LN in adult-onset SLE [ 110 , 111 ], and more recently in JSLE, correlating positively with the level of proteinuria, and the SLEDAI, renal SLEDAI, and SLICC renal activity scores, and negatively with C3 serum levels [ 95 ]. In this study, the normalised urinary sCD25 levels were higher in JSLE patients than in healthy controls, and in JSLE patients with active LN compared to active JSLE patients without LN [ 95 ].…”