title: Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1β secretion in response to anti-MPO antibodies.
abstract: ANCA vasculitis encompasses several autoimmune conditions characterised by destruction of small vessels, inflammation of the respiratory tract and glomerulonephritis. Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3). Clinical and experimental data suggest that pathogenesis is driven by ANCA-mediated activation of neutrophils and monocytes. We investigated a potential role for distinct monocyte subsets. We found that the relative proportion of intermediate monocytes is increased in patients versus control individuals, and both MPO and PR3 are preferentially expressed on these cells. We demonstrate that MPO and PR3 are expressed independently of each other on monocytes and that PR3 is not associated with CD177. MPO expression correlates with that of Fc receptor CD16 on intermediate monocytes. Monocyte subsets respond differently to antibodies directed against MPO and PR3, with anti-MPO but not anti-PR3 leading to increased IL-1β, IL-6 and IL-8 production. In concordance with the observed higher surface expression of MPO on intermediate monocytes, this subset produces the highest quantity of IL-1β in response to anti-MPO stimulation. These data suggest that monocytes, specifically, the intermediate subset, may play a role in ANCA vasculitis, and also indicate that substantial differences exist between the effect of anti-MPO and anti-PR3 antibodies on these cells.
authors.affiliation: Trinity Health Kidney Centre, Department of Clinical Medicine, Trinity College Dublin, St. James' Hospital Campus, Dublin 8, Ireland.
authors.forename: Eóin C
authors.initials: EC
authors.lastname: O'Brien
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Wayel H
authors.initials: WH
authors.lastname: Abdulahad
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Abraham
authors.initials: A
authors.lastname: Rutgers
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Minke G
authors.initials: MG
authors.lastname: Huitema
authors.affiliation: Trinity Health Kidney Centre, Department of Clinical Medicine, Trinity College Dublin, St. James' Hospital Campus, Dublin 8, Ireland.
authors.forename: Vincent P
authors.initials: VP
authors.lastname: O'Reilly
authors.affiliation: Trinity Health Kidney Centre, Department of Clinical Medicine, Trinity College Dublin, St. James' Hospital Campus, Dublin 8, Ireland.
authors.forename: Alice M
authors.initials: AM
authors.lastname: Coughlan
authors.affiliation: Trinity Health Kidney Centre, Department of Clinical Medicine, Trinity College Dublin, St. James' Hospital Campus, Dublin 8, Ireland.
authors.forename: Mark
authors.initials: M
authors.lastname: Harrington
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
authors.affiliation: Trinity Health Kidney Centre, Department of Clinical Medicine, Trinity College Dublin, St. James' Hospital Campus, Dublin 8, Ireland.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Little
authors.affiliation: Trinity Health Kidney Centre, Department of Clinical Medicine, Trinity College Dublin, St. James' Hospital Campus, Dublin 8, Ireland.
authors.forename: Fionnuala B
authors.initials: FB
authors.lastname: Hickey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000378:metabolism; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007519:Isoantigens / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D053146:Myeloblastin / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D009195:Peroxidase / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D011961:Receptors, Fc / Q000737:chemistry / Q000378:metabolism; D017452:Receptors, IgG / Q000737:chemistry / Q000378:metabolism; D014657:Vasculitis / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D001324:Autoantigens; C407242:CD177 protein, human; D058851:GPI-Linked Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D007519:Isoantigens; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; D017452:Receptors, IgG; D009195:Peroxidase; D053146:Myeloblastin