Chronic rhinosinusitis with nasal polyps is characterized by B-cell inflammation and EBV-induced protein 2 expression

• Published in: Journal of allergy and clinical immunology Vol. 131; no. 4; pp. 1075 - 1083.e7
• Main Authors: Hulse, Kathryn E., Norton, James E., Suh, Lydia, Zhong, Qiu, Mahdavinia, Mahboobeh, Simon, Patrick, Kern, Robert C., Conley, David B., Chandra, Rakesh K., Tan, Bruce K., Peters, Anju T., Grammer, Leslie C., Harris, Kathleen E., Carter, Roderick G., Kato, Atsushi, Schleimer, Robert P.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.04.2013; Elsevier; Elsevier Limited
• Subjects: Adult; Age; Aged; Allergy and Immunology; antibodies; Antibodies - immunology; B cells; B-Lymphocytes - immunology; B-Lymphocytes - pathology; Biological and medical sciences; Biomarkers - metabolism; Case-Control Studies; Cell Lineage - immunology; Chronic Disease; chronic inflammation; Chronic rhinosinusitis; correlation; Disease; EBV-induced protein 2 (EBI2); enzyme-linked immunosorbent assay; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; genes; Humans; Immune system; Immunohistochemistry; Immunopathology; inflammation; Inflammation - immunology; Inflammation - pathology; Laboratories; Male; Medical sciences; Methods; Middle Aged; morbidity; Nasal Polyps - immunology; Nasal Polyps - pathology; Non tumoral diseases; nose; Otolaryngology; Otorhinolaryngology. Stomatology; Pathogenesis; patients; plasma cells; Plasma Cells - immunology; Plasma Cells - pathology; polyps (pathological conditions); Positive Regulatory Domain I-Binding Factor 1; protein synthesis; Proteins; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - immunology; Repressor Proteins - genetics; Repressor Proteins - immunology; reverse transcriptase polymerase chain reaction; Rhinitis - genetics; Rhinitis - immunology; Rhinitis - pathology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sinuses; Sinusitis - genetics; Sinusitis - immunology; Sinusitis - pathology; Surgery; Syndecan-1 - genetics; Syndecan-1 - immunology; tissues; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Western blotting; NP; Chronic rhinosinusitis; CRS; IHC; EBI2; DAPI; CRSwNP; B cells; plasma cells; CRSsNP; pIgR; CH25H; EBV-induced protein 2 (EBI2); antibodies; chronic inflammation; hpf; UT; Immunohistochemistry; Nasal polyp; 4′-6-Diamidino-2-pnehnylindole dihydrochloride; EBV-induced protein 2; Cholesterol 25-hydroxylase; High-power field; Chronic rhinosinusitis without nasal polyps; Polymeric immunoglobulin receptor; Chronic rhinosinusitis with nasal polyps; Uncinate tissue; Nose disease; Rhinitis; Upper respiratory tract; Epstein Barr virus; Plasmocyte; Sinusitis; Immunology; ENT disease; Gammaherpesvirinae; Immunopathology; Antibody; Herpesviridae; Inflammation; B-Lymphocyte; Protein; Infection; Virus; Chronic; Viral disease; Paranasal sinus disease
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2013.01.043

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. 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. 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. 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. 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.