title: Chronic rhinosinusitis with nasal polyps is characterized by B-cell inflammation and EBV-induced protein 2 expression.
abstract: BACKGROUND
  Despite the high prevalence and morbidity of chronic rhinosinusitis (CRS), little is known about the mechanisms that underlie its pathogenesis. Recent studies have suggested that B cells might play an important role in CRS.
  
  
  OBJECTIVE
  We sought to thoroughly characterize B lineage cells within sinus tissues of patients with CRS and healthy control subjects and to determine whether levels of EBV-induced protein 2, which is known to play an important role in the development of B-cell responses, were increased in patients with CRS.
  
  
  METHODS
  Cells isolated from sinus tissues of patients with CRS and healthy control subjects were characterized by means of flow cytometry and immunohistochemistry. Local production of antibodies was measured in tissue extracts, nasal lavage fluid, and sera by using multiplex bead arrays and ELISA. Quantitative RT-PCR, ELISA, and Western blotting were used to assess gene and protein expression from tissue extracts.
  
  
  RESULTS
  Nasal polyps (NPs) from patients with CRS had increased levels of both B cells and plasma cells compared with uncinate tissue from healthy control subjects (P<.05). NPs also contained significantly increased levels of several antibody isotypes compared with normal uncinate tissue (P<.05), but no differences in circulating antibody levels were found. Interestingly, levels of EBV-induced protein 2 were also increased in NPs (P<.05) and were positively correlated with expression of plasma cell markers (CD138 and B lymphocyte-induced maturation protein) in sinus tissue.
  
  
  CONCLUSIONS
  B cells and plasma cells are enriched in NPs, actively produce antibodies locally, and might contribute to chronic inflammation in patients with CRS. Elucidating the mechanisms that underlie this excessive local B-cell response might provide novel insights for the development of improved therapeutic strategies.
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Hulse
authors.forename: James E
authors.initials: JE
authors.lastname: Norton
authors.forename: Lydia
authors.initials: L
authors.lastname: Suh
authors.forename: Qiu
authors.initials: Q
authors.lastname: Zhong
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Mahdavinia
authors.forename: Patrick
authors.initials: P
authors.lastname: Simon
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kern
authors.forename: David B
authors.initials: DB
authors.lastname: Conley
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Chandra
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Tan
authors.forename: Anju T
authors.initials: AT
authors.lastname: Peters
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Grammer
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Harris
authors.forename: Roderick G
authors.initials: RG
authors.lastname: Carter
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Robert P
authors.initials: RP
authors.lastname: Schleimer
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D019070:Cell Lineage / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000276:immunology / Q000473:pathology*; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology; D012220:Rhinitis / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D012852:Sinusitis / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D053668:Syndecan-1 / Q000235:genetics / Q000276:immunology
chemical_list: D000906:Antibodies; D015415:Biomarkers; C080105:GPR183 protein, human; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; C508241:SDC1 protein, human; D053668:Syndecan-1; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1