A NEUTROPHIL DEGRANULATION SIGNATURE IDENTIFIES PROLIFERATIVE LUPUS NEPHRITIS.
- Andrea Fava (United States of America)
Abstract
Background and Aims
The identification of intrarenal pathological processes is key to develop better diagnostic and treatment strategies in lupus nephritis (LN). The direct study of renal tissue can be limited by degradation, availability, and cell survival. We employed urine proteomics to define the molecular pathways involved in proliferative LN.
Methods
We quantified 1200 biomarkers (RayBiotech) in urine samples collected on the day of (73%) or within 3 weeks (27%) of kidney biopsy in SLE patients with urine protein to creatinine ratio on random or 24 hr collection of > .5. Protein concentrations were normalized by urine creatinine.
Results
A total of 195 patients were included: 138 (71%) had a proliferative histological class (III or IV +/- V), 57 (29%) pure membranous (V). There were 21 (FDR 1%) differentially abundant urinary proteins in proliferative compared to pure membranous LN (Figure 1A). These included several neutrophil granule proteins (Figure 1B) in addition to previously reported biomarkers such as IL-16 and CD163. Unsupervised clustering based on the proliferative LN signature identified 3 groups characterized by low, medium or high protein abundance (Figure 2). Higher proliferative signature abundance (right cluster) was associated with higher histological activity (NIH Activity Index). Immunofluorescence confirmed an abundant MPO+ neutrophil infiltrate in proliferative LN (Figure 3).
Conclusions
Proliferative LN was associated with a urinary neutrophil degranulation signature, especially in patients with higher histological activity. Neutrophil activity could be noninvasively monitored to assist with the diagnosis of proliferative LN. These findings implicate neutrophils in LN pathogenesis and support the study of treatment targeted to neutrophils.
