Abstract: SA-OR023
Infiltrating Citrullinated Histone (CitH3)-Positive Neutrophils May Be Involved in Active Glomerular and Interstitial Lesions in ANCA-Related Vasculitis
Session Information
- ANCA It Is
November 09, 2019 | Location: 207, Walter E. Washington Convention Center
Abstract Time: 04:54 PM - 05:06 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Kimura, Hidehito, Nippon medical school, Tokyo, Japan
- Mii, Akiko, Nippon Medical School, Tokyo, Japan
- Arakawa, Yusuke, Nippon Medical School, Tokyo, Japan
- Tsuruoka, Shuichi, Nippon Medical School, Tokyo, Japan
- Shimizu, Akira, Nippion 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 is unknown. Citrullination of histones is an essential step for NETs formation, and the presence of citrullinated histones (CitH3) in neutrophils may be involved in disease induction and activity. We examined an association between infiltrating neutrophils with/without CitH3 and disease specificity and activity in various glomerulonephritis (GN).
Methods
We selected following cases, who presented proliferative GN with neutrophil infiltration; AAV (n=8), lupus nephritis (LN) (n=5), Henoch schonlein purpura nephritis (HSPN) (n=5), and post-streptococcal acute GN (PSAGN) (n=5). We assessed clinical characteristics and histopathological findings and examined myeloperoxidase (MPO)-positive (+) infiltrating neutrophils with or without CitH3 in glomeruli and interstitium and association with the necrotizing and crescentic glomerular lesions and tubulointerstitial lesions.
Results
Number of MPO+ neutrophils in glomeruli was significantly higher in PSAGN, LN and HSPN than in AAV. In LN, MPO+ neutrophils were found mainly on the margin of glomerular tufts which formed wire-loop lesions. In part of them, CitH3+ neutrophils were seen. In PSAGN and HSPN, many MPO+ infiltrated in glomeruli, however, only a few CitH3+ neutrophils. In contrast, the frequency of CitH3+ neutrophils in AAV was significantly higher while the number of MPO+ neutrophils was significantly lower than in other diseases. CitH3+ neutrophils were observed in necrotizing lesion along glomerular capillaries. Moreover, the frequency of CitH3+ neutrophils was significantly higher not only in glomeruli but also in interstitium than in the others. In addition, peritubular capillaritis with CitH3+ neutrophils was remarkable.
Conclusion
CitH3 immunostaining was useful tool for identifying activated neutrophils. In AAV cases, the frequency of CitH3+ neutrophils in both glomeruli and interstitium was significantly higher. The frequency of CitH3+ neutrophils is not only a disease specific marker but also a possibility of becoming a marker for disease activity in AVV.