title: CD14 expression is increased on monocytes in patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis and correlates with the expression of ANCA autoantigens.
abstract: Monocyte subsets with differing functional properties have been defined by their expression of CD14 and CD16. We investigated these subsets in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and determined their surface expression of ANCA autoantigens. Flow cytometry was performed on blood from 14 patients with active AAV, 46 patients with AAV in remission and 21 controls. The proportion of classical (CD14(high) CD16(neg/low)), intermediate (CD14(high) CD16(high)) and non-classical (CD14(low) CD16(high)) monocytes and surface expression levels of CD14 and CD16 were determined, as well as surface expression of proteinase 3 (PR3) and myeloperoxidase (MPO) on monocyte subsets. There was no change in the proportion of monocytes in each subset in patients with AAV compared with healthy controls. The expression of CD14 on monocytes from patients with active AAV was increased, compared with patients in remission and healthy controls (P < 0.01). Patients with PR3-ANCA disease in remission also had increased monocyte expression of CD14 compared with controls (P < 0.01); however, levels in patients with MPO-ANCA disease in remission were lower than active MPO-ANCA patients, and not significantly different from controls. There was a correlation between CD14 and both PR3 and MPO expression on classical monocytes in AAV patients (r = 0.79, P < 0.0001 and r = 0.42, P < 0.005, respectively). In conclusion, there was an increase in monocyte CD14 expression in active AAV and PR3-ANCA disease in remission. The correlation of CD14 expression with ANCA autoantigen expression in AAV may reflect cell activation, and warrants further investigation into the potential for increased CD14 expression to trigger disease induction or relapse.
authors.affiliation: Renal and Vascular Inflammation Section, Department of Medicine, Imperial College London, London, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Tarzi
authors.affiliation: Renal and Vascular Inflammation Section, Department of Medicine, Imperial College London, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Renal and Vascular Inflammation Section, Department of Medicine, Imperial College London, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Schneiter
authors.affiliation: Renal and Vascular Inflammation Section, Department of Medicine, Imperial College London, London, UK.
authors.forename: N R
authors.initials: NR
authors.lastname: Hill
authors.affiliation: Renal and Vascular Inflammation Section, Department of Medicine, Imperial College London, London, UK.
authors.forename: T H
authors.initials: TH
authors.lastname: Page
authors.affiliation: Renal and Vascular Inflammation Section, Department of Medicine, Imperial College London, London, UK.
authors.forename: H T
authors.initials: HT
authors.lastname: Cook
authors.affiliation: Renal and Vascular Inflammation Section, Department of Medicine, Imperial College London, London, UK.
authors.forename: C D
authors.initials: CD
authors.lastname: Pusey
authors.affiliation: Renal and Vascular Inflammation Section, Department of Medicine, Imperial College London, London, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Woollard
mesh_terms: D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000096:biosynthesis*; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000096:biosynthesis; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D053146:Myeloblastin / Q000096:biosynthesis; D009195:Peroxidase / Q000096:biosynthesis; D017452:Receptors, IgG / Q000096:biosynthesis*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D009195:Peroxidase; D053146:Myeloblastin
keywords: anti-neutrophil cytoplasm antibody (ANCA); monocyte; myeloperoxidase (MPO); proteinase 3 (PR3)