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

Abstract

Background: Lupus nephritis (LN) is a prevalent and severe complication of systemic lupus erythematosus (SLE). Non-invasive diagnostics are limited, and current therapies have inadequate response rates. Expression of the chemokine Interferon-γ-induced protein 10 (IP-10) is regulated by Interferon-γ signaling and NF-κB, and its molecular activity and enhanced urine concentrations are implicated in LN, but its utility as a diagnostic marker and association with demographic, clinical, or pathologic features is not defined. Methods: 38 LN patients and 11 patients with non-LN glomerular diseases (GD) with active disease were included. Eighteen of the LN patients had achieved remission at one follow-up during the study time. Serum and urine were obtained from these samples, and the IP-10 levels were measured. Results: Serum and urine IP-10 levels are significantly enhanced in LN patients with active disease as compared with normal individuals (serum average 179.7 pg/mL vs. 7.2 pg/mL, p < 0.0001; urine average 28.7 pg/mg vs. 1.6 pg/mg, p = 0.0019) and patients with other forms of glomerular disease (serum average 179.7 pg/mL vs. 84.9 pg/mL, p = 0.0176; urine average 28.7 pg/mg vs. 0.18 pg/mg, p = 0.0011). Urine IP-10 levels are significantly higher in patients with proliferative LN (PLN) than those with membranous LN (MLN) (average 32.8 pg/mg vs. 7.6 pg/mg, p = 0.0155). Urine IP-10 levels are also higher in MLN versus primary membranous nephropathy (MN) (average 7.6 pg/mg vs. 0.2 pg/mg, p = 0.0193). Importantly, serum IP-10 levels remain elevated during active LN and LN remission, but urine IP-10 levels are decreased from active LN to remission in 72% of our patients. Lastly, serum, but not urine IP-10 levels are significantly higher in African American than White American LN patients in active LN (average 227.8 pg/mL vs. 103.4 pg/mL, p = 0.0309) and during LN remission (average 254.6 pg/mL vs. 89.2 pg/mL, p = 0.0399). Conclusions: Our findings suggest that serum and urine IP-10 measurements provide promising tests for monitoring LN activity, differentiation between classifications of LN, and differentiation between LN and other forms of glomerular disease. We also conclude that further assessment of elevated IP-10 levels in the serum and urine of high-risk populations (i.e., African American) could be beneficial in determining why many of these patients have worse outcomes and are non-responsive to standard therapeutics.

B‐ and T‐Lymphocyte Attenuator in Systemic Lupus Erythematosus Disease Pathogenesis

“…BAFF and IP10 genes were added to several analyses for comparison. BAFF is a target of the approved therapeutic antibody against SLE, and IP10 is a widely known disease activity marker in SLE 32,33 . In addition, the association of BTLA and HVEM expression with indicators of SLE disease activity was assessed to determine if there is a therapeutic rationale for activating BTLA in SLE.…”

Predicting systemic lupus erithematosus disease activity index 2000 (Sledai 2k) score after pulse dose metyl prednisolone in severe systemic lupus erithematosus

“…8 IP-10 levels are significantly higher in the acute phase of SLE. 9 Additionally, SLE treatment modalities such as prednisolone, mycophenolate, and hydroxychloroquine significantly lower serum IP-10 levels. 10 The goal of this study is to use clinical manifestations, routine laboratory examinations, and more specific protein examinations such as sBAFF, BAFF-R, and IP-10 to predict SLEDAI 2k score following pulse-dose MEP, given that the spectrum of clinical manifestations and response to treatment varies from patient to patient.…”