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Abstract: SA-PO935

Citrullinated Histone H3-Positive Neutrophils May Be Associated with Disease Activity in ANCA-Associated Vasculitis

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Kamijo, Natsumi, Nihon Ika Daigaku, Bunkyo-ku, Tokyo, Japan
  • Mii, Akiko, Nihon Ika Daigaku, Bunkyo-ku, Tokyo, Japan
  • Nakazato, Rei, Nihon Ika Daigaku, Bunkyo-ku, Tokyo, Japan
  • Shimizu, Akira, Nihon Ika Daigaku, Bunkyo-ku, Tokyo, Japan
  • Sakai, Yukinao, Nihon Ika Daigaku, Bunkyo-ku, Tokyo, Japan
Background

Neutrophil extracellular traps (NETs) formation is reportedly involved in the onset of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Citrullinated histone H3 (H3Cit) is an important component of NETs. Previously, we reported that the presence of H3Cit (+) neutrophils is more specific in AAV than in other glomerular diseases and H3Cit staining is useful for identifying activated neutrophils. However, there were no detailed analysis of association between H3Cit neutrophils and AAV disease activity.

Methods

We selected kidney biopsy cases with AAV at Nippon Medical School Hospital during 2011 to 2022. Clinical findings included age, gender, serum creatinine (sCr) level, CRP, MPO/PR3-ANCA titer, and urinary findings (urinary protein (U-P) level, urinary β2-microglobulin (uβ2-MG)). Histological findings were assessed as follows: rates of global sclerotic glomeruli, crescent formation, interstitial fibrosis, and atherosclerosis score). MPO (neutrophil marker) and H3Cit (NETs marker) staining were performed.

Results

A total of 49 cases with AAV were selected and were divided into two groups : H3Cit (+) group (n=44) and H3Cit (-) group (n=5) according to the presence or absence of H3Cit+ neutrophils in renal tissues.
Clinically, sCr level and uβ2-MG level were significantly higher in the H3Cit (+) group although there were no significant differences in age, CRP, ANCA titer and U-P level. Histologically, H3Cit (+) neutrophils were observed in tubulointerstitial lesions in 43 cases, and in both tubulointerstitial lesions and glomeruli in 13 cases. Only one case showed glomerular involvement.
H3Cit (+) neutrophils were observed mainly in peritubular capillaries, and around necrotic lesions of arteries and glomeruli. The rates of crescent formation and interstitial fibrosis were significantly higher in the H3Cit (+) group while there was no differences in rates of global sclerotic glomeruli and atherosclerosis score.

Conclusion

The H3Cit (+) group exhibited significantly worse renal function and urinary findings, as well as higher tissue activity. The presence of H3Cit+ neutrophils serves not only a disease-specific marker but also a potential indicator of disease activity in AAV.