title: Classical complement pathway activation in the nasal tissue of patients with chronic rhinosinusitis.
abstract: BACKGROUND
  Complement plays a major role in inflammatory diseases, but its involvement and mechanisms of activation in patients with chronic rhinosinusitis (CRS) are not known.
  
  
  OBJECTIVE
  After earlier studies discovering autoantibodies in patients with CRS, we sought to investigate the nature, extent, and location of complement activation in nasal tissue of patients with CRS. Specifically, we were interested in whether antibody-mediated activation through the classical pathway was a major mechanism for complement activation in patients with CRS.
  
  
  METHODS
  Nasal tissue was obtained from patients with CRS and control subjects. Tissue homogenates were analyzed for complement activation products (ELISA-C5b-9, C4d, activated C1, and C5a) and major complement-fixing antibodies (Luminex). Tissue sections were stained for C5b-9, C4d, and laminin. Antibodies were purified with protein A/G columns from nasal polyps (NP), matching patient serum, and control serum and assayed for basement membrane binding by means of ELISA.
  
  
  RESULTS
  C5b-9 levels were significantly increased in NP tissue compared with uncinate tissue (UT) of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and those with chronic rhinosinusitis without nasal polyps (CRSsNP; P < .01). Similarly, C4d levels were increased in NPs compared with UT of patients with CRSwNP, patients with CRSsNP, and control subjects (P < .05). Activated C1 levels were also increased in NP tissue compared with UT of patients with CRSsNP and control subjects (P < .05) and correlated with levels of C5a (P < .01), local immunoglobulins (especially IgM, P < .0001), and anti-double-stranded DNA IgG (P < .05). Immunofluorescence showed that C5b-9 and C4d deposition occurred linearly along the epithelial basement membrane. NP tissue extracts had significantly more anti-basement membrane antibodies than sera from patients with CRSwNP and control subjects (P < .0001).
  
  
  CONCLUSIONS
  Levels of C5b-9, C4d, and activated C1 were significantly increased locally in NP tissue. C5b-9 and C4d were almost universally deposited linearly along the basement membrane of NP tissue. Furthermore, activated C1 levels were best correlated with local immunoglobulin and C5a levels. Together, these data suggest that the classical pathway plays a major role in complement activation in patients with CRS.
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Griet A
authors.initials: GA
authors.lastname: Van Roey
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Vanison
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Jeffanie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Julia H
authors.initials: JH
authors.lastname: Huang
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Lydia A
authors.initials: LA
authors.lastname: Suh
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Roderick G
authors.initials: RG
authors.lastname: Carter
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: James E
authors.initials: JE
authors.lastname: Norton
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Shintani-Smith
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: David B
authors.initials: DB
authors.lastname: Conley
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Welch
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Anju T
authors.initials: AT
authors.lastname: Peters
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Grammer
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Harris
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Hulse
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Whitney W
authors.initials: WW
authors.lastname: Stevens
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kern
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Schleimer
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address: b-tan@northwestern.edu.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Tan
mesh_terms: D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000276:immunology; D002908:Chronic Disease; D003171:Complement Pathway, Classical; D004802:Eosinophilia / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology*; D009298:Nasal Polyps / Q000276:immunology*; D012220:Rhinitis / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G
keywords: Chronic rhinosinusitis; antibodies; basement membrane; classical complement pathway; complement