title: Granulomatosis with polyangiitis involves sustained mucosal inflammation that is rich in B-cell survival factors and autoantigen.
abstract: OBJECTIVE
  Granulomatosis with polyangiitis (GPA) is a rare chronic autoimmune disease that may be triggered by upper airway infection. ANCAs specific for PR3 that is expressed by activated neutrophils and macrophages are associated with GPA. Our aim was to investigate regional immune mechanisms that might induce or support the autoimmune response in GPA.
  
  
  METHODS
  Biopsy samples from 77 patients including 8 with GPA were studied by immunohistochemistry. B-cell homing subsets in blood samples from 16 patients with GPA and 11 healthy controls were studied by FACS. The distribution of B-cell clones was searched in paired biopsies and blood samples from one patient by analysing immunoglobulin heavy chain gene (IGH) junctional sequences.
  
  
  RESULTS
  Activated B cells were located alongside PR3-expressing cells and B-cell survival factors BAFF and APRIL in mucosa from patients with GPA. We detected APRIL production by the granulomas and giant cells. B cells were proliferating in all cases and persistent for 5 years in biopsies obtained from one patient. However, there was no evidence of B-cell clones from the mucosal biopsies circulating in peripheral blood in GPA or any numerical or proportional change in B-cell subsets expressing markers of regional homing in blood in GPA.
  
  
  CONCLUSIONS
  Our study illustrates chronically activated B cells alongside autoantigens and B-cell survival factors in the mucosa in GPA.
authors.affiliation: Peter Gorer Department of Immunobiology, Guy's Hospital, London, UK.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Edward
authors.initials: E
authors.lastname: Odell
authors.forename: Lee Meng
authors.initials: LM
authors.lastname: Choong
authors.forename: Francesca
authors.initials: F
authors.lastname: Barone
authors.forename: Paul
authors.initials: P
authors.lastname: Fields
authors.forename: Bridget
authors.initials: B
authors.lastname: Wilkins
authors.forename: Fahim M
authors.initials: FM
authors.lastname: Tungekar
authors.forename: Pritash
authors.initials: P
authors.lastname: Patel
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Sanderson
authors.forename: Shirish
authors.initials: S
authors.lastname: Sangle
authors.forename: David
authors.initials: D
authors.lastname: D'Cruz
authors.forename: Jo
authors.initials: J
authors.lastname: Spencer
mesh_terms: D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics / Q000276:immunology; D014890:Granulomatosis with Polyangiitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D001324:Autoantigens; D015415:Biomarkers