AB0508 Serum and Urinary Interferon-Gamma-Inducible Protein 10 in Lupus Nephritis

Abstract

BackgroundLupus nephritis (LN) is one of the serious complications of systemic lupus erythematosus (SLE). Finding reliable non-invasive biomarkers for LN will help to improve disease outcomes. IFN-γ-inducible protein 10 (IP-10) is a pro-inflammatory chemokines which is involved in the immunopathogenesis of LN. Thus, we investigated the role of IP-10 as a potential marker of LN.ObjectivesTo identify the sensitivity, specificity and cut-off value of serum and urinary IP-10 level in LN patients compared to albumin/creatinine ratio and anti-dsDNA.MethodsWe included 30 female SLE patients and 10 age-matched healthy female controls. SLE disease activity index (SLEDAI) was calculated. Active SLE was defined as SLEDAI ≥4. Patients were divided into 10 SLE patients with LN, 10 active SLE without LN and 10 inactive SLE patients. Serum and urinary levels of IP-10 were measured by ELISA. Anti-dsDNA and urine albumin/creatinine ratio were measured. Renal biopsy was performed to LN patients.ResultsMean age of patients was 30±10 years versus 32±9 years in controls. Mean disease duration was 52±16 months. Mean SLEDAI was 10.2±3.6.Active SLE patients had significantly increased serum IP-10 (324±224 pg/dl) and urinary IP-10 (172±206 pg/dl) as compared to inactive SLE (215±188 pg/dl and 121±150 pg/dl respectively) (P<0.01) and healthy controls (103±28 pg/dl and 32±13 pg/dl respectively) (P<0.008).No significant difference was found in serum and urinary IP-10 levels between active LN and active non-renal patients, even in biopsy-proved proliferative LN patients.Serum and urinary IP-10 positively correlated with SLEDAI (r=0.416; P<0.02) and (r=0.448, P<0.01) respectively.By receiver operating characteristics (ROC) analysis, serum and urinary IP-10 could be used to diagnose SLE with serum IP-10 being better [p=0.011, AUC, 95% confidence interval (CI) = 0.772 {0.629–0.915}, P=0.018, AUC 95% CI = 0.753 (0.606–0.901) respectively].A value of serum IP-10 116.5 pg/ml as a cut-off value is best in differentiating SLE patients from healthy controls with 76% sensitivity and 70% specificity. A value of urinary IP-10 37.9 pg/ml is best in indicating SLE with 70% sensitivity and 70% specificity.Serum IP-10 could differentiate active from inactive SLE [P=0.007, AUC (95% CI = 0.753 (0.594–0.911)]. It is better than urinary IP-10, albumin/creatinine ratio and anti-dsDNA [AUC {95% CI = 0.654 (0.467–0.841); {0.529 (0.317–0.742)} {607 (402–812)}].A value of serum IP-10 136 pg/ml is best in differentiating active from inactive SLE with 81% sensitivity and 71% specificity.Serum and urinary IP-10 did not significantly differentiate either LN from SLE without LN [AUC 95% CI = 0.633 (0.430–0.837), 0.610 (0.397–0.823)], nor active renal SLE from active non renal SLE (AUC [95% CI = 0.533 (0.230–0.837), 0.700 (0.431–0.969)].Albumin/creatinine ratio is a better marker in differentiating between SLE with LN and SLE without LN [P=0.008, AUC (95% CI = 0.803 (0.610–0.995)]Any of the serum and urinary IP-10, albumin/ creatinine ratio, and anti-dsDNA didn't correlate...

Serum and Urine Interferon Gamma-Induced Protein 10 (IP-10) Levels in Lupus Nephritis

“…Defining improved noninvasive diagnostics and novel therapeutic targets for lupus nephritis (LN) will facilitate better disease management, and studies have implicated interferon (IFN)-γ-induced protein 10 (IP-10) as a candidate serum and urine marker for autoimmune activity and LN in SLE patients [ 9 , 10 , 11 , 12 , 13 ]. A meta-analysis published in 2019 thoroughly analyzed and reviewed data from 15 reports presenting serum and/or urine IP-10 protein levels in the context of disease activity in SLE patients [ 14 ].…”

“…T cells, neutrophils, monocytes, and endothelial cells secrete IP-10, and enhanced serum levels are reported in a number of systemic autoimmune diseases, including rheumatoid arthritis, systemic sclerosis, and SLE [ 7 , 8 ]. A role for IP-10 in LN is implicated from several reports showing enhanced IP-10 mRNA or protein levels in serum, urine, kidney biopsies, or circulating immune cells in patients with SLE with active LN [ 9 , 10 , 11 , 12 , 13 ]. A recent meta-analysis of studies investigating IP-10 as a potential biomarker for SLE/LN concluded that urinary, but not serum levels of IP-10 were significantly elevated in patients with active-LN versus active-SLE/without LN [ 14 ].…”