Background
Lupus nephritis (LN) occurs in more than half of patients with systemic lupus erythematosus, but the cellular and molecular events that contribute to LN are not clearly defined. We reported previously that neutrophil degranulation participates in glomerular injury in mouse models of acute LN. This study tests the hypothesis that glomerular recruitment and subsequent activation of neutrophils result in urine excretion of neutrophil granule constituents that are predictive of glomerular inflammation in proliferative LN.
Conclusions
Circulating neutrophils in patients with LN are primed for enhanced degranulation. Glomerular recruitment of those primed neutrophils leads to release and urine excretion of neutrophil granule cargo that serves as a urine marker of active glomerular inflammation in proliferative LN.
Methods
Urine and serum levels of 11 neutrophil granule proteins were measured by antibody-based array in patients with proliferative LN and healthy donors (HDs), and the
Results
Eight granule proteins (myeloperoxidase, neutrophil elastase, azurocidin, olfactomedin-4, lactoferrin, alpha-1-acid glycoprotein 1, matrix metalloproteinase 9, and cathelicidin) were significantly elevated in urine from patients with active proliferative LN by array and/or ELISA, whereas only neutrophil elastase was increased in LN serum. Urine excretion of alpha-1-acid glycoprotein 1 declined in patients who achieved remission. The majority of LN glomeruli contained ≥3 neutrophils. Basal levels of specific granule markers were increased in neutrophils from patients with LN compared with HD controls. Serum from patients with active LN stimulated specific and secretory, but not azurophilic granule, release by HD neutrophils. Conclusions: Circulating neutrophils in patients with LN are primed for enhanced degranulation. Glomerular recruitment of those primed neutrophils leads to release and urine excretion of neutrophil granule cargo that serves as a urine marker of active glomerular inflammation in proliferative LN.