LAUSR

OBJECTIVES To investigate the expression of type I interferon (IFN-I) and neutrophil transcripts in kidney tissue from patients with different classes of lupus nephritis and their association with distinct clinical and histopathological features. METHODS Quantitation of IFN-I, defensin-α3 and formyl peptide receptor-like 1 (FPRL-1) transcripts was performed in kidney biopsy tissue from 24 patients with various classes of lupus nephritis (6 class III, 14 class IV, 4 class V) and 3 control samples. Patient demographics, glomerular filtration rate (eGFR) and histopathological characteristics, including activity and chronicity indices were analyzed. RESULTS IFNα2 and IFNβ transcripts were overexpressed in renal tissues from patients with proliferative forms of lupus nephritis (III/IV) compared with patients with membranous nephritis and control kidneys. Patients with lupus nephritis and impaired renal function, attested by eGFR, displayed higher relative expression of IFNα2 transcripts in renal tissues compared with those with normal renal function (23.0 ± 16.2 vs 12.0 ± 14.8, p= 0.04). Defensin-α3, but not FPRL-1, transcripts were overexpressed in lupus nephritis tissues, particularly those with segmental necrotizing lesions, and were correlated with higher renal pathological activity indices (r = 0.61, p= 0.02), urinary protein levels (r = 0.48, p= 0.04) and IFNα2 expression (r = 0.50, p= 0.01). CONCLUSION IFN-I transcripts are expressed locally in kidneys from patients with proliferative lupus nephritis and associated with impaired renal function. Elevated defensin-α3 transcripts, a neutrophil product associated with neutrophil extracellular traps, may identify a driver of local IFN-I expression. These findings provide insight into the mechanisms of proliferative lupus nephritis and may inform therapeutic decisions regarding selection of IFN-I pathway inhibitors.