Kidney-infiltrating proteinase 3-positive granulocytes are abundant in lupus nephritis.

Authors

Alessandra Ida Celia, Chen-Yu Lee, Xiaoping Yang, Taibo Li, Kelly Casella, Angelique Cortez, Cristiano Alessandri, Fabrizio Conti, Eugene Shenderov, Michelle Petri, Sladjana Skopelja-Gardner, Avi Rosenberg, Andrea Fava

Published in

Rheumatology (Oxford, England). Jul 17, 2026. Epub Jul 17, 2026.

Abstract

Active proliferative lupus nephritis (LN) is associated with elevated urinary neutrophil granule proteins such as proteinase 3 (PR3), implicating active cellular degranulation in LN. Yet, mature neutrophils are rarely observed in LN biopsies, raising the possibility of an unrecognized cellular source. We aimed to identify and characterize PR3-expressing myeloid cells in LN kidneys using a spatially resolved multi-omics approach.
Serial immunohistochemistry (10-plex) and spatial transcriptomics were employed to assess the distribution of PR3+ cells across renal tissue and characterize their cellular phenotype.
PR3+ cells were abundant in LN kidney biopsies, but with marked inter-patient heterogeneity. These cells were predominantly localized to the tubulointerstitium and showed similar distribution in both proliferative and membranous LN. In contrast, intraglomerular PR3+ cells were enriched in proliferative LN and correlated with the NIH Activity Index. Phenotype analysis identified four subsets of PR3+ cells, consistent with a monocyte/neutrophil lineage. Most PR3+ cells lacked multilobate nuclei, distinguishing them from mature neutrophils, suggesting that these cells may be overlooked by conventional light microscopy.
PR3+ myeloid cells are a prominent and heterogeneous population in lupus nephritis. While intraglomerular PR3+ cells were specific to proliferative LN and correlated with histologic activity, the widespread presence of PR3+ cells in the tubulointerstitium suggests broader involvement in renal inflammation than previously recognized. These findings reveal a potentially overlooked immune cell population that may contribute to renal injury in LN.

PMID:
42467826
Bibliographic data and abstract were imported from PubMed on 18 Jul 2026.

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