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

Kathryn E. Hulse, James E. Norton, Lydia Suh, Qiu Zhong, Mahboobeh Mahdavinia, Patrick Simon, Robert C. Kern, David B. Conley, Rakesh K. Chandra, Bruce K. Tan, Anju T. Peters, Leslie C. Grammer, Kathleen E. Harris, Roderick G. Carter, Atsushi Kato, Robert P. Schleimer*

*Corresponding author for this work

Research output: Contribution to journalArticle

63 Citations (Scopus)

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. Conclusion: 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.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
Volume131
Issue number4
DOIs
StatePublished - Jan 1 2013

Fingerprint

Nasal Polyps
Human Herpesvirus 4
B-Lymphocytes
Inflammation
Plasma Cells
Healthy Volunteers
Proteins
Tissue Extracts
Antibodies
Enzyme-Linked Immunosorbent Assay
Nasal Lavage Fluid
Antibody Formation
Flow Cytometry
Western Blotting
Immunohistochemistry
Morbidity
Gene Expression
Polymerase Chain Reaction
Serum

Keywords

  • B cells
  • Chronic rhinosinusitis
  • EBV-induced protein 2 (EBI2)
  • antibodies
  • chronic inflammation
  • plasma cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

@article{be9dce5bd8004cc08cf888ea193bd073,
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. Conclusion: 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.",
keywords = "B cells, Chronic rhinosinusitis, EBV-induced protein 2 (EBI2), antibodies, chronic inflammation, plasma cells",
author = "Hulse, {Kathryn E.} and Norton, {James E.} and Lydia Suh and Qiu Zhong and Mahboobeh Mahdavinia and Patrick Simon and Kern, {Robert C.} and Conley, {David B.} and Chandra, {Rakesh K.} and Tan, {Bruce K.} and Peters, {Anju T.} and Grammer, {Leslie C.} and Harris, {Kathleen E.} and Carter, {Roderick G.} and Atsushi Kato and Schleimer, {Robert P.}",
year = "2013",
month = "1",
day = "1",
doi = "10.1016/j.jaci.2013.01.043",
language = "English (US)",
volume = "131",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
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Chronic rhinosinusitis with nasal polyps is characterized by B-cell inflammation and EBV-induced protein 2 expression. / 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.

In: Journal of Allergy and Clinical Immunology, Vol. 131, No. 4, 01.01.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Chronic rhinosinusitis with nasal polyps is characterized by B-cell inflammation and EBV-induced protein 2 expression

AU - Hulse, Kathryn E.

AU - Norton, James E.

AU - Suh, Lydia

AU - Zhong, Qiu

AU - Mahdavinia, Mahboobeh

AU - Simon, Patrick

AU - Kern, Robert C.

AU - Conley, David B.

AU - Chandra, Rakesh K.

AU - Tan, Bruce K.

AU - Peters, Anju T.

AU - Grammer, Leslie C.

AU - Harris, Kathleen E.

AU - Carter, Roderick G.

AU - Kato, Atsushi

AU - Schleimer, Robert P.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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. Conclusion: 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.

AB - 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. Conclusion: 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.

KW - B cells

KW - Chronic rhinosinusitis

KW - EBV-induced protein 2 (EBI2)

KW - antibodies

KW - chronic inflammation

KW - plasma cells

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U2 - 10.1016/j.jaci.2013.01.043

DO - 10.1016/j.jaci.2013.01.043

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JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

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ER -