Kidney Week

Abstract: TH-PO828

Urinary Galectin-3 Binding Protein as a Predictive Marker for Lupus Nephritis Flare

Session Information

• Glomerular Diseases: Immunology and Inflammation - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Parikh, Samir V., Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Samir V. Parikh,

• Zhang, Xiaolan, Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Xiaolan Zhang,

• Bassi, Roberto, EMD Serono R&D Institute, Rockland, Massachusetts, United States

Roberto Bassi,

• Varghese, Sneha, EMD Serono R&D Institute, Rockland, Massachusetts, United States

Sneha Varghese,

• Mehta, Pramod P., MilliporeSigma, St Louis, Missouri, United States

Pramod P. Mehta,

• Lie, Wen-Rong, MilliporeSigma, St Louis, Missouri, United States

Wen-Rong Lie,

• Okitsu, Shinji L., EMD Serono Research and Development Institute, Billerica, Massachusetts, United States

Shinji L. Okitsu,

• Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Brad H. Rovin,

Background

Identifying predictive markers of lupus nephritis (LN) flare has been elusive but is necessary to improve outcomes. Serum galectin-3 binding protein (G3BP) is correlated with interferon signature in active SLE. We aimed to define the specificity of urine G3BP (uG3BP) as marker of LN flare and determine its ability to predict flare and response to treatment.

Methods

uG3BP protein expression was measured from urine collected at the time of kidney biopsy and compared across multiple glomerular diseases including active LN (n=97), IgA nephropathy (n=27), diabetic nephropathy (n=10), primary membranous nephropathy (n=10), ANCA-associated vasculitis (n=4) and healthy controls (n=20). Additionally, active LN expression was compared to LN remission (n=52). uG3BP levels were normalized for urinary creatinine (Cr). To examine uG3BP expression longitudinally, urine from the Ohio SLE cohort study (OSS) of 27 LN patients (44 flares) was measured by ELISA at 5 different time points; -4, -2, flare, +2, and +4 months post flare. uG3BP expression was compared between each time point to understand if uG3BP is a sensitive marker to predict the development and resolution of inflammation in LN.

Results

uG3BP expression was significantly increased in all tested kidney diseases, except ANCA compared to healthy controls (p<0.0001). The highest concentration of uG3BP was found in active LN (423.79±32.06 ng G3BP/mg Cr). uG3BP expression was significantly greater at LN flare compared to controls (423.79±32.06 vs 44.8 ng G3BP/mg cr, p<0.0001), IgA nephropathy (423.79±32.06 vs 138 ng G3BP/mg Cr, p<0.0001) and remisison LN (423.79±32.06 vs127.5 ng G3BP/mg Cr, p<0.0001). uG3BP expression increased incrementally from 4 months pre-flare to flare, peaked 2 months post-flare (p=0.02 compared to flare levels) and significantly decreased 4 months post-flare (p=0.01).

Conclusion

uG3BP, while not specific, is highly expressed at LN flare reflecting interferon activation. uG3BP expression may predict LN flare but due to limited samples size data are currently inconclusive. Further investigation is warranted. uG3BP expression may be a predictive marker of treatment response.

Funding

• Commercial Support –