Presenting Author:

Scott Feldman, M.D.

Principal Investigator:

Kathryn Hulse, Ph.D.

Department:

Medicine

Keywords:

chronic sinusitis, nasal polyps, B cells, B lymphocytes, plasmablasts, innate lymphoid cells, B cell activation, Epstein... [Read full text] chronic sinusitis, nasal polyps, B cells, B lymphocytes, plasmablasts, innate lymphoid cells, B cell activation, Epstein–Barr virus-induced protein 2 [Shorten text]

Location:

Third Floor, Feinberg Pavilion, Northwestern Memorial Hospital

B37 - Basic Science

Antibody-Secreting Cells are Elevated in CRSwNP Patients Correlating with Complement

Rationale: We have previously reported elevated levels of activated B cells and antibodies in nasal polyps (NP) from patients with chronic rhinosinusitis with NP (CRSwNP). We sought to investigate the mechanisms driving B cell activation and antibody production in NP. Methods: NP or tonsil tissue were obtained from CRSwNP or non-CRS patients, respectively. Activated complement products were measured by ELISA, and the frequency of antibody-secreting cells was assessed using ELISpot assays. B cell subsets were characterized by flow cytometry. Antibody production in vitro was measured from culture supernatants after ex vivo tissue explant culture. Local B cell activation and class switch recombination were determined by measuring expression of activation-induced cytidine deaminase (AID), and gamma, alpha, and epsilon germline transcripts. Results: Flow cytometry analysis revealed significantly elevated levels of antibody-secreting cells in NP compared to tonsil (p<0.01). Additionally, NP tissue explants produced significantly more antibodies than tonsil (3-10 fold increase, p<0.05). In NP, we found detectable expression of AID plus epsilon, gamma, and alpha germline transcripts. Finally, the frequency of IgG- (3-fold), IgA- (20-fold), and IgE- (20-fold) secreting cells in NP was significantly elevated (p<0.05). The frequency of IgG- and IgA-secreting cells was positively correlated with levels of activated complement products C1 and C5b-9 in the tissue (p<0.01). Conclusions: These data support the hypothesis that B cells in NP are highly activated and secrete large amounts of antibodies, suggesting a relationship between activated B cells, antibody production, and complement activation that could contribute to CRSwNP pathogenesis.