TY - JOUR
T1 - A panel of urinary proteins predicts active lupus nephritis and response to rituximab treatment
AU - BILAG-BR
AU - MRC MASTERPLANS Consortia
AU - Davies, Jennifer C.
AU - Carlsson, Emil
AU - Midgley, Angela
AU - Smith, Eve M.D.
AU - Bruce, Ian N.
AU - Beresford, Michael W.
AU - Hedrich, Christian M.
AU - Lunt, Mark
AU - Prattley, Jennifer
AU - Azadbakht, Narges
AU - Doherty, Patrick
AU - Armitt, Gillian
AU - Farrelly, Carmen
AU - Hewitt, Lauren
AU - Payne, Katherine
AU - Gavan, Sean
AU - Geifman, Nophar
AU - Vital, Edward
AU - Pickering, Matthew
AU - Ehrenstein, Michael
AU - McHugh, Neil
AU - Gordon, Caroline
AU - Reynolds, John
AU - Farewell, Vern
AU - Su, Li
AU - Jayne, David
AU - Vyse, Tim
AU - Youssef, Hazem
AU - Paton, Pamela
AU - Shotton, Julie
AU - Hall, Frances
AU - Willcocks, Lisa
AU - Jones, Rachel
AU - Jordan, Natasha
AU - McClure, Mark
AU - Trivedi, Sapna
AU - Flint, Shaun
AU - McKinney, Eoin
AU - Stober, Carmel
AU - Smith, Rona
AU - Coles, Alisdair
AU - Cahill, Hugh
AU - Cox, Amanda
AU - Burns, Stella
AU - Hollis, Jane
AU - Tordesillas, Hugo
AU - Goymer, Donna
AU - Hadavi, Shahryar
AU - Evans, Jobie
AU - Perry, Mark
N1 - Publisher Copyright:
© 2020 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
PY - 2021/8/1
Y1 - 2021/8/1
N2 - Objectives: ∼30% of patients with SLE develop LN. Presence and/or severity of LN are currently assessed by renal biopsy, but biomarkers in serum or urine samples may provide an avenue for non-invasive routine testing. We aimed to validate a urinary protein panel for its ability to predict active renal involvement in SLE. Methods: A total of 197 SLE patients and 48 healthy controls were recruited, and urine samples collected. Seventy-five of the SLE patients had active LN and 104 had no or inactive renal disease. Concentrations of lipocalin-like prostaglandin D synthase (LPGDS), transferrin, alpha-1-acid glycoprotein (AGP-1), ceruloplasmin, monocyte chemoattractant protein 1 (MCP-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were quantified by MILLIPLEX® Assays using the MAGPIX Luminex platform. Binary logistic regression was conducted to examine whether proteins levels associate with active renal involvement and/or response to rituximab treatment. Results: Urine levels of transferrin (P <0.005), AGP-1 (P <0.0001), MCP-1 (P <0.001) and sVCAM-1 (P <0.005) were significantly higher in SLE patients when compared with healthy controls. Furthermore, levels of transferrin, AGP-1, ceruloplasmin, MCP-1 and sVCAM-1 (all P <0.0001) were higher in SLE patients with active LN when compared with patients without active LN. A combination of five urine proteins, namely LPGDS, transferrin, ceruloplasmin, MCP-1 and sVCAM-1 was a good predictor of active LN (AUC 0.898). A combined model of LPGDS, transferrin, AGP-1, ceruloplasmin, MCP-1 and sVCAM-1 predicted response to rituximab treatment at 12 months (AUC 0.818). Conclusions: Findings support the use of a urinary protein panel to identify active LN and potentially predict response to treatment with rituximab in adult SLE patients. Prospective studies are required to confirm findings.
AB - Objectives: ∼30% of patients with SLE develop LN. Presence and/or severity of LN are currently assessed by renal biopsy, but biomarkers in serum or urine samples may provide an avenue for non-invasive routine testing. We aimed to validate a urinary protein panel for its ability to predict active renal involvement in SLE. Methods: A total of 197 SLE patients and 48 healthy controls were recruited, and urine samples collected. Seventy-five of the SLE patients had active LN and 104 had no or inactive renal disease. Concentrations of lipocalin-like prostaglandin D synthase (LPGDS), transferrin, alpha-1-acid glycoprotein (AGP-1), ceruloplasmin, monocyte chemoattractant protein 1 (MCP-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were quantified by MILLIPLEX® Assays using the MAGPIX Luminex platform. Binary logistic regression was conducted to examine whether proteins levels associate with active renal involvement and/or response to rituximab treatment. Results: Urine levels of transferrin (P <0.005), AGP-1 (P <0.0001), MCP-1 (P <0.001) and sVCAM-1 (P <0.005) were significantly higher in SLE patients when compared with healthy controls. Furthermore, levels of transferrin, AGP-1, ceruloplasmin, MCP-1 and sVCAM-1 (all P <0.0001) were higher in SLE patients with active LN when compared with patients without active LN. A combination of five urine proteins, namely LPGDS, transferrin, ceruloplasmin, MCP-1 and sVCAM-1 was a good predictor of active LN (AUC 0.898). A combined model of LPGDS, transferrin, AGP-1, ceruloplasmin, MCP-1 and sVCAM-1 predicted response to rituximab treatment at 12 months (AUC 0.818). Conclusions: Findings support the use of a urinary protein panel to identify active LN and potentially predict response to treatment with rituximab in adult SLE patients. Prospective studies are required to confirm findings.
KW - biomarker
KW - inflammation
KW - lupus nephritis
KW - renal
KW - rituximab
KW - SLE
KW - stratification
KW - treatment
UR - https://www.scopus.com/pages/publications/85113708759
U2 - 10.1093/rheumatology/keaa851
DO - 10.1093/rheumatology/keaa851
M3 - Article
C2 - 33313921
AN - SCOPUS:85113708759
SN - 1462-0324
VL - 60
SP - 3747
EP - 3759
JO - Rheumatology
JF - Rheumatology
IS - 8
ER -