title: The influence of cathelicidin LL37 in human anti-neutrophils cytoplasmic antibody (ANCA)-associated vasculitis.
abstract: BACKGROUND
  Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterised by the autoinflammation and necrosis of blood vessel walls. The renal involvement is commonly characterised by a pauci-immune crescentic glomerulonephritis (PiCGN) with a very rapid decline in renal function. Cathelicidin LL37, an endogenous antimicrobial peptide, has recently been implicated in the pathogenesis of autoimmune diseases. To assess whether serum LL37 reflects renal crescentic formation, we measured the serum levels of LL37 in AAV patients with and without crescentic glomerulonephritis (crescentic GN) as compared to healthy controls (HCs). We also analysed the correlation of the serum levels of LL37 and interferon-α (IFN-α) with the clinical characteristics of the patients.
  
  
  METHODS
  The study population consisted of 85 AAV patients and 51 HCs. In 40 ANCA-positive patients, a parallel analysis was performed, including the assessment of LL37 and IFN-α levels in the serum and renal biopsies. Of those studied, 15 AAV patients had biopsy-proven crescentic GN, and 25 AAV patients lacked crescent formation. The serum levels of cathelicidin LL37 and IFN-α were both measured by ELISA, and the clinical and serological parameters were assessed according to routine procedures. Immunofluorescence staining was performed on frozen sections of kidney needle biopsies from AAV patients with crescentic GN.
  
  
  RESULTS
  The serum levels of LL37 and IFN-α were significantly increased in AAV patients with crescentic GN compared to AAV patients without crescentic formation and HCs, and patients with high LL37 and IFN-α levels were more likely to be in the crescentic GN group. The LL37 levels were positively correlated with the IFN-α levels, and both LL37 and IFN-α levels showed a positive correlation with serum creatinine and no correlation with complement C3. The renal tissue of crescentic GN patients showed expression of LL37 and IFN-α at the Bowman's capsule and extracellular sites, suggesting the active release of LL37 and IFN-α.
  
  
  CONCLUSIONS
  Significantly higher levels of LL-37 and IFN-α were observed in AAV patients, particularly those with crescentic formation, and LL37 and IFN-α were expressed in the renal tissue of patients with crescentic GN. These data suggest that serum levels of LL37 and IFN-α may reflect both local renal inflammation and systemic inflammation.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Shi
authors.forename: Sha
authors.initials: S
authors.lastname: Tang
authors.forename: Jingyi
authors.initials: J
authors.lastname: Li
authors.forename: Shiwei
authors.initials: S
authors.lastname: Yin
authors.forename: Xuejing
authors.initials: X
authors.lastname: Gao
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Liyun
authors.initials: L
authors.lastname: Zou
authors.forename: Jinghong
authors.initials: J
authors.lastname: Zhao
authors.forename: Yunjian
authors.initials: Y
authors.lastname: Huang
authors.forename: Lianyu
authors.initials: L
authors.lastname: Shan
authors.forename: Abdelilah S
authors.initials: AS
authors.lastname: Gounni
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
authors.forename: Fahuan
authors.initials: F
authors.lastname: Yuan
authors.forename: Jingbo
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood* / Q000150:complications / Q000276:immunology; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D001706:Biopsy; D054804:Cathelicidins / Q000097:blood*; D002478:Cells, Cultured; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005921:Glomerulonephritis / Q000150:complications* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000097:blood; D007668:Kidney / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D010446:Peptide Fragments / Q000097:blood*; D055815:Young Adult
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D054804:Cathelicidins; D016898:Interferon-alpha; D010446:Peptide Fragments; C534394:cathelicidin LL-37 (18-29), human