Background Conventional serological markers do not always correlate with clinical activity in lupus nephritis (LN). CD44 is a transmembrane glycoprotein that is widely expressed in immune and non-immune cells, and is implicated in tissue inflammation and fibrosis. CD44 also serves as a cell receptor for hyaluronan (HA), a glycosaminoglycan that contributes to inflammatory and fibrosis processes. This study investigated clinico-pathological associations of circulating CD44 level.
Methods Serial serum samples from patients with biopsy-proven Class III/IV LN were collected at intervals of 3–4 months over 3 to 4 years. Sera from sex- and age-matched patients with non-renal SLE or non-lupus chronic kidney disease (CKD) or healthy subjects served as Controls. Serum CD44 level was measured by ELISA
Results Six hundred and sixty-seven sera from 41 patients with LN (31 female and 10 male, age 38.78±12.02 years) were included. Serum CD44 level was significantly higher in active LN compared to remission, non-renal SLE, CKD, or healthy subjects (P<0.001, for all). Serum CD44 level correlated with SLEDAI-2K and renal SLEDAI-2K scores, anti-dsDNA antibody titre, proteinuria, and serum HA level, and inversely correlated with eGFR and C3 level (P<0.001, for all). Serum CD44 level increased at the time of nephritic flare and decreased after treatment with immunosuppression. A temporal relationship was observed between CD44 level and SLEDAI-2K or renal SLEDAI-2K scores, anti-dsDNA antibody and C3 levels, and proteinuria. ROC analysis showed that serum CD44 level distinguished active LN from healthy subjects (sensitivity 98.31%, specificity 100.00%), from quiescent LN (sensitivity 86.44%, specificity 98.31%), from non-renal SLE (sensitivity 98.31%, specificity 95.24%), and from non-lupus CKD (sensitivity 98.31%, specificity 100.00%) (P<0.0001, for all).
Conclusions Active LN is associated with increased serum CD44 level. Further studies are required to determine whether CD44 can serve as a clinically useful biomarker in the diagnosis and monitoring of LN activity.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.