title: Characterization of immunoglobulin E plasma cells that are elevated in the upper airway mucosa of nonatopic patients with chronic rhinosinusitis without nasal polyps.
abstract: BACKGROUND
  The immunologic mechanisms driving inflammation in the upper airways of patients with chronic rhinosinusitis (CRS) are poorly understood. Previous studies have shown that B cells and immunoglobulin E (IgE) levels are elevated in the nasal tissue of patients with atopic chronic rhinosinusitis without nasal polyps (CRSsNP). However, less is known regarding B cell subsets and IgE-producing plasmablasts in nonatopic CRSsNP patients.
  
  
  METHODS
  Human blood and ethmoid sinus mucosa samples were analyzed from control (n = 6) and nonatopic CRSsNP (n = 11) patients. Tissue samples were evaluated using high-dimensional flow cytometry.
  
  
  RESULTS
  A population of IgE antibody secreting cells is significantly increased in situ within inflamed nasal tissue of nonatopic CRSsNP subjects when compared to control nasal tissue and the circulating peripheral blood (p < 0.05). This IgE plasma cell population displays ∼90% cell surface Ig lambda light chain, is mitotically active (Ki-67(+)), and displays intracellular IgE expression. The predominant B cell population expressing IgE are plasmablasts (CD38(high), CD138(-)) not typically found in the blood or peripheral tissue of these patients.
  
  
  CONCLUSIONS
  The nasal mucosa from nonatopic CRSsNP patients demonstrate a significant regional spike in resident in situ IgE plasmablast cells not seen in control nasal tissue or peripheral blood from the same patient. The restricted expression of Ig lambda light chain in this mitotically active IgE plasmablast population supports the hypothesis of aberrant B cell proliferation in the context of CRS. These findings suggest the presence of a unique regional immune microenvironment for B cell priming and/or selection within chronically inflamed airway tissues.
authors.affiliation: Division of Rhinology, Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA.
authors.forename: Ali R
authors.initials: AR
authors.lastname: Rashan
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA.
authors.forename: Eliver
authors.initials: E
authors.lastname: Goshn
authors.affiliation: Division of Rhinology, Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA.
authors.forename: Asa
authors.initials: A
authors.lastname: Peterson
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA.
authors.forename: Meghan
authors.initials: M
authors.lastname: Phillips
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA.
authors.forename: Bita
authors.initials: B
authors.lastname: Sahaf
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA.
authors.forename: Leonore
authors.initials: L
authors.lastname: Herzenberg
authors.affiliation: Division of Rhinology, Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA.
authors.forename: Jayakar V
authors.initials: JV
authors.lastname: Nayak
mesh_terms: D002908:Chronic Disease; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology*; D009298:Nasal Polyps; D010950:Plasma Cells / Q000276:immunology*; D012220:Rhinitis / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*
chemical_list: D007073:Immunoglobulin E
keywords: B cell; CD138; CD38; FACS; IgE; PBMC; chronic rhinosinusitis; flow cytometry; nasal mucosa; plasmablast; upper airway