Neutrophils associate with Bowman's capsule rupture specifically in PR3-ANCA glomerulonephritis

Abstract

Background: Renal involvement is a common and severe complication of ANCA (antineutrophil cytoplasmic antibody) associated vasculitis (AAV) potentially resulting in a pauci-immune necrotizing and crescentic antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis (GN) with acute kidney injury (AKI), end-stage renal disease (ESRD) or death. We recently described that Bowman's capsule rupture links glomerular damage to tubulointerstitial inflammation in ANCA-associated glomerulonephritis. Herein we provide a comprehensive histological subtyping of immune cell infiltrates in association with Bowman's capsule rupture in ANCA GN.

Methods: A total of 44 kidney biopsies with ANCA GN were retrospectively included in a single-center observational study. Within a renal biopsy specimen, each glomerulus was scored separately for the presence of extensive and focal Bowman's capsule rupture in injured glomeruli. Infiltrates of neutrophils, eosinophils, plasma cells, and mononucleated cells (macrophages, lymphocytes) were quantified as a fraction of the area of total cortical inflammation.

Results: Extensive Bowman's capsule rupture was associated with tubulointerstitial inflammation containing infiltrates of neutrophils, eosinophils and plasma cells. A similar association was observed for the presence of focal Bowman's capsule rupture, correlating with tubulointerstitial inflammation containing neutrophils, eosinophils and plasma cells. Multiple logistic regression confirmed that extensive Bowman's capsule rupture correlated with tubulointerstitial inflammation containing neutrophils, and focal Bowman's capsule rupture correlated with neutrophil and plasma cell infiltration. Furthermore, this association was specifically observed in PR3-ANCA GN.

Conclusion: To our knowledge, this is the first report linking Bowman's capsule rupture directly to tubulointerstitial inflammation by immune cell subtypes. This underscores a pathomechanistic link between tubulointerstitial and glomerular lesions in ANCA GN and needs further investigation.

Keywords: ANCA glomerulonephritis; Bowman’s capsule rupture; Neutrophils; Tubulointerstitial inflammation.

Fig. 1

Tubulointerstitial inflammation containing neutrophils associates with BCR in ANCA GN. A Representative Elastica van Gieson-stained renal biopsy in ANCA GN (scale bar: 50 µm). B Representative periodic acid-Schiff reaction-stained renal biopsy in ANCA GN with BCR (scale bar: 50 µm). C, D The association between the fraction of glomeruli affected by extensive or focal BCR, and subtypes of immune cell infiltrates in ANCA GN is shown by a heatmap reflecting mean values of Spearman’s ρ, corresponding values of p are shown. ANCA anti-neutrophil cytoplasmic antibodies, BCR Bowman’s capsule rupture, GN glomerulonephritis, MPO myeloperoxidase, PR3 proteinase 3

Fig. 2

Tubulointerstitial inflammation containing neutrophils associates with BCRspecifically in PR3-ANCA GN. A, B Association between the fraction of glomeruli affected by extensive BCR and subtypes of immune cell infiltrates separated for PR3-ANCA and MPO-ANCA GN is shown by a heatmap reflecting mean values of Spearman’s ρ, corresponding values of p are shown. C, D The association between the fraction of glomeruli affected by focal BCR and subtypes of immune cell infiltrates separated for PR3-ANCA and MPO-ANCA GN is shown by a heatmap reflecting mean values of Spearman’s ρ, corresponding values of p are shown. ANCA anti-neutrophil cytoplasmic antibodies, BCR Bowman’s capsule rupture, GN glomerulonephritis, MPO myeloperoxidase, PR3 proteinase 3