Serum and Urine Interferon Gamma-Induced Protein 10 (IP-10) Levels in Lupus Nephritis
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...
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MDPI AG
2022-06-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/11/3199 |
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| author | Makayla P. Brady Saiteja Chava Shweta Tandon Madhavi J. Rane Michelle T. Barati Dawn J. Caster David W. Powell |
| author_facet | Makayla P. Brady Saiteja Chava Shweta Tandon Madhavi J. Rane Michelle T. Barati Dawn J. Caster David W. Powell |
| author_sort | Makayla P. Brady |
| collection | DOAJ |
| description | 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, <i>p</i> < 0.0001; urine average 28.7 pg/mg vs. 1.6 pg/mg, <i>p</i> = 0.0019) and patients with other forms of glomerular disease (serum average 179.7 pg/mL vs. 84.9 pg/mL, <i>p</i> = 0.0176; urine average 28.7 pg/mg vs. 0.18 pg/mg, <i>p</i> = 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, <i>p</i> = 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, <i>p</i> = 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, <i>p</i> = 0.0309) and during LN remission (average 254.6 pg/mL vs. 89.2 pg/mL, <i>p</i> = 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. |
| first_indexed | 2024-03-10T01:10:38Z |
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| language | English |
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| spelling | doaj.art-ba36641206e84207b649ed7970f64e3b2023-11-23T14:18:30ZengMDPI AGJournal of Clinical Medicine2077-03832022-06-011111319910.3390/jcm11113199Serum and Urine Interferon Gamma-Induced Protein 10 (IP-10) Levels in Lupus NephritisMakayla P. Brady0Saiteja Chava1Shweta Tandon2Madhavi J. Rane3Michelle T. Barati4Dawn J. Caster5David W. Powell6Department of Biochemistry and Molecular Genetics, School of Medicine, University of Louisville, Louisville, KY 40202, USADepartment of Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USADepartment of Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USADepartment of Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USADepartment of Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USADepartment of Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USADepartment of Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USABackground: 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, <i>p</i> < 0.0001; urine average 28.7 pg/mg vs. 1.6 pg/mg, <i>p</i> = 0.0019) and patients with other forms of glomerular disease (serum average 179.7 pg/mL vs. 84.9 pg/mL, <i>p</i> = 0.0176; urine average 28.7 pg/mg vs. 0.18 pg/mg, <i>p</i> = 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, <i>p</i> = 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, <i>p</i> = 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, <i>p</i> = 0.0309) and during LN remission (average 254.6 pg/mL vs. 89.2 pg/mL, <i>p</i> = 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.https://www.mdpi.com/2077-0383/11/11/3199systemic lupus erythematosuslupus nephritisurinary biomarkersserum biomarkersIP10interferon |
| spellingShingle | Makayla P. Brady Saiteja Chava Shweta Tandon Madhavi J. Rane Michelle T. Barati Dawn J. Caster David W. Powell Serum and Urine Interferon Gamma-Induced Protein 10 (IP-10) Levels in Lupus Nephritis Journal of Clinical Medicine systemic lupus erythematosus lupus nephritis urinary biomarkers serum biomarkers IP10 interferon |
| title | Serum and Urine Interferon Gamma-Induced Protein 10 (IP-10) Levels in Lupus Nephritis |
| title_full | Serum and Urine Interferon Gamma-Induced Protein 10 (IP-10) Levels in Lupus Nephritis |
| title_fullStr | Serum and Urine Interferon Gamma-Induced Protein 10 (IP-10) Levels in Lupus Nephritis |
| title_full_unstemmed | Serum and Urine Interferon Gamma-Induced Protein 10 (IP-10) Levels in Lupus Nephritis |
| title_short | Serum and Urine Interferon Gamma-Induced Protein 10 (IP-10) Levels in Lupus Nephritis |
| title_sort | serum and urine interferon gamma induced protein 10 ip 10 levels in lupus nephritis |
| topic | systemic lupus erythematosus lupus nephritis urinary biomarkers serum biomarkers IP10 interferon |
| url | https://www.mdpi.com/2077-0383/11/11/3199 |
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