Cross-sectional study of plasma Axl, ferritin, IGFBP4 and sTNFR2 as biomarkers of disease activity in childhood-onset SLE: A study of the Pediatric Nephrology Research Consortium

• Type of Material: Article
• Authors: Samar A Soliman, University of Houston; Anam Haque, University of Houston; Sherene Mason, Connecticut Children’s Medical Center; Larry Greenbaum, Emory University; John M Hicks, Texas Children’s Hospital; Chandra Mohan, University of Houston; Scott E Wenderfer, Texas Children’s Hospital
• Language: English
• Date: 2021-05-14
• Publisher: SAGE PUBLICATIONS LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © The Author(s) 2021.
• Final Published Version (URL): http://dx.doi.org/10.1177/09612033211016100
• Title of Journal or Parent Work: LUPUS
• Volume: 30
• Issue: 9
• Start Page: 1394
• End Page: 1404
• Grant/Funding Information: NIH R01 AR074096
• Keywords: Science & Technology; NEPHRITIS; ALPHA; kidney diseases; RECEPTOR TYROSINE KINASE; lupus erythematosus; Life Sciences & Biomedicine; GROWTH; biomarkers; INDEX; proteomics; pediatrics; Lupus nephritis; MARKERS; SERUM FERRITIN; SOLUBLE AXL; systemic; CLASSIFICATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; Rheumatology

Abstract

Objective: To evaluate the performance of 4 plasma protein markers for detecting disease activity in childhood-onset systemic lupus erythematosus (SLE) patients. Methods: Eighty-three consecutive pediatric patients fulfilling ≥4 ACR criteria for SLE and twenty-five healthy controls were prospectively recruited for serological testing of 4 protein markers identified by antibody-coated microarray screen, namely Axl, ferritin, IGFBP4 and sTNFR2. SLE disease activity was assessed using SLEDAI-2000 score. Fifty-seven patients had clinically active SLE (SLEDAI score ≥4, or having a flare). Results: The plasma concentrations of Axl and ferritin were significantly higher in patients with active SLE than inactive SLE. Plasma Axl levels were significantly higher in active renal versus active non-renal SLE patients. Levels of Axl, ferritin and IGFBP4 correlated significantly with SLEDAI scores. Levels of Axl, IFGBP4 and sTNFR2 inversely correlated with plasma complement C3 levels. Only plasma Axl and ferritin levels correlated with degree of proteinuria. These markers were more specific, but less sensitive, in detecting concurrent SLE activity than elevated anti-dsDNA antibody titer or decreased C3. Ferritin and IGFBP4 levels were more specific for concurrent active lupus nephritis than anti-dsDNA or C3. Plasma ferritin was the best monitor of global SLE activity, followed by C3 then Axl, while both Axl and C3 were best monitors of clinical lupus nephritis activity. Conclusion: In childhood-onset SLE patients, plasma ferritin and Axl perform better than traditional yardsticks in identifying disease activity, either global or renal. The performance of these plasma markers should be explored further in longitudinal cohorts of SLE patients.