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Abstract: SA-PO1081

Impact of Infiltrating Neutrophils’ Phenotype on Disease Activity in Various Glomerulonephritis

Session Information

Category: Pathology and Lab Medicine

  • 1502 Pathology and Lab Medicine: Clinical

Authors

  • Kimura, Hidehito, Nippon medical school, Tokyo, Japan
  • Mii, Akiko, Nippon Medical School, Tokyo, Japan
  • Arakawa, Yusuke, Nippon Medical School, Tokyo, Japan
  • Shimizu, Akira, Nippion Medical School, Tokyo, Japan
  • Tsuruoka, Shuichi, Nippon Medical School, Tokyo, Japan
Background

Activated neutrophils release neutrophil extracellular traps (NETs), resulting in cell death called NETosis. NETs formation has been reported to be involved in the onset of systemic lupus erythematosus and ANCA-related vasculitis (AAV). However, the precise mechanism remains unclear. Citrullination of histones is an essential step for NETs formation, and the presence of citrullinated histones in neutrophils may be involved in disease induction and activity. We investigated the association between infiltrating neutrophils with/without citrullinated histone and disease activity in various glomerulonephritis (GN).

Methods

We selected kidney biopsy samples of AAV, lupus nephritis (LN), Henoch schonlein purpura nephritis (HSPN), and acute post-streptococcal GN (APSGN)(n = 5, each), which presented proliferative GN with neutrophil infiltration in glomeruli and interstitium. To identify infiltrating neutrophils and citrullinated histones, we performed immunostaining for myeloperoxidase (MPO) and citrullinated histone H3 (CitH3), and assessed the frequency of citrullinated histone positive neutrophils in glomeruli and interstitium.

Results

Number of MPO+ neutrophils in glomeruli tends to be higher in APSGN, LN and HSPN than in AAV. In APSGN and HSPN, however, CitH3+ neutrophils were very few in their endocapillary proliferative lesions in glomeruli. In addition, a few MPO+ neutrophils and CitH3+ neutrophils infiltrated the interstitium. In LN and AAV, CitH3+ neutrophils were observed in necrotizing lesion and wire-loop lesion along glomerular capillaries. Moreover, in AAV, the frequency of CitH3+ neutrophils in both glomeruli and interstitium was significantly higher than the others and correlated with crescent formation.

Conclusion

CitH3 immunostaining was useful tool for identifying activated neutrophils. In addition, it was suggested that there was correlation disease activity of GN with the frequency of activated neutrophils.