CD163: a potential biomarker for lupus nephritis activity
Erdem Gürel, Suzan Çinar, Özge Hürdogan, Yasemin Özlük, Gamze Kemeç, Ömer Uludağ, Sibel Varelci, Safak Mirioğlu, Yasemin Yalçinkaya, Ahmet Gül, Murat Inanç, Bahar Artim-EsenObjectives
CD163 is a macrophage-associated scavenger receptor shed during inflammatory activation, resulting in measurable soluble CD163 in serum (s) and urine (u). Elevated levels have been reported in inflammatory and immune-mediated conditions, including lupus nephritis (LN). This study aimed to investigate the relationship between soluble CD163 levels and intrarenal CD163 expression, evaluating their association with disease activity and treatment response in LN.
Methods
Forty-five patients with systemic lupus erythematosus (SLE) were included (20 active LN, 10 inactive LN, 15 active extra-renal SLE), together with 20 matched healthy controls. Serum and urine samples were collected at baseline alongside renal biopsy in active LN; 6-month follow-up samples were available for 12 active LN patients. CD163 was measured by ELISA; urinary CD163 was normalised to spot urine creatinine. Renal biopsies from 20 active LN patients were evaluated for CD163+ macrophage density.
Results
uCD163 was higher in active LN (a renal Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) flare (UPCR ≥0.5 g/g) with biopsy-proven active lesions) than in inactive LN and active extra-renal SLE (both p<0.001), discriminating active from inactive LN (area under the curve (AUC) 0.97) and from extra-renal SLE (AUC 0.89). uCD163 correlated with the National Institutes of Health activity and chronicity indices activity index (ρ=0.55, p=0.016) and with glomerular CD163+ macrophage density (the number of CD163+ macrophages per glomerulus quantified by immunohistochemistry; ρ=0.65, p=0.006), but not with chronicity. Glomerular CD163+ macrophage density also correlated with sCD163 (ρ=0.60, p=0.01) and uCD163 (ρ=0.63, p=0.009). After 6-month induction, uCD163 fell from 7.41 to 1.55 ng/mg (p<0.001).
Conclusion
uCD163 distinguishes active LN from inactive renal and extra-renal disease and tracks treatment response. The association with intrarenal CD163+ macrophages supports its biological relevance as a non-invasive marker of renal inflammation, complementary to histopathology when repeat biopsy is not feasible. These findings support uCD163 as a candidate non-invasive tool for identifying active LN and monitoring treatment response in SLE, warranting validation in larger prospective cohorts.