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Abstract
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.
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