Chronic rhinosinusitis with nasal polyps is characterized by B-cell inflammation and EBV-induced protein 2 expression
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...
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| Published in | Journal of allergy and clinical immunology Vol. 131; no. 4; pp. 1075 - 1083.e7 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York, NY
Mosby, Inc
01.04.2013
Elsevier Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0091-6749 1097-6825 1097-6825 |
| DOI | 10.1016/j.jaci.2013.01.043 |
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| Abstract | 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. |
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| AbstractList | 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. 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.BACKGROUNDDespite 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.OBJECTIVEWe 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.METHODSCells 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.RESULTSNasal 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.CONCLUSIONB 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. 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. 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 ( < .05). NPs also contained significantly increased levels of several antibody isotypes compared with normal uncinate tissue ( < .05), but no differences in circulating antibody levels were found. Interestingly, levels of EBV-induced protein 2 were also increased in NPs ( < .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. 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. 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. |
| Author | Zhong, Qiu Simon, Patrick Carter, Roderick G. Kern, Robert C. Hulse, Kathryn E. Chandra, Rakesh K. Tan, Bruce K. Suh, Lydia Mahdavinia, Mahboobeh Harris, Kathleen E. Schleimer, Robert P. Conley, David B. Norton, James E. Grammer, Leslie C. Kato, Atsushi Peters, Anju T. |
| AuthorAffiliation | a Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine b Department of Otolaryngology, Northwestern University Feinberg School of Medicine |
| AuthorAffiliation_xml | – name: a Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine – name: b Department of Otolaryngology, Northwestern University Feinberg School of Medicine |
| Author_xml | – sequence: 1 givenname: Kathryn E. surname: Hulse fullname: Hulse, Kathryn E. organization: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 2 givenname: James E. surname: Norton fullname: Norton, James E. organization: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 3 givenname: Lydia surname: Suh fullname: Suh, Lydia organization: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 4 givenname: Qiu surname: Zhong fullname: Zhong, Qiu organization: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 5 givenname: Mahboobeh surname: Mahdavinia fullname: Mahdavinia, Mahboobeh organization: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 6 givenname: Patrick surname: Simon fullname: Simon, Patrick organization: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 7 givenname: Robert C. surname: Kern fullname: Kern, Robert C. organization: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 8 givenname: David B. surname: Conley fullname: Conley, David B. organization: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 9 givenname: Rakesh K. surname: Chandra fullname: Chandra, Rakesh K. organization: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 10 givenname: Bruce K. surname: Tan fullname: Tan, Bruce K. organization: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 11 givenname: Anju T. surname: Peters fullname: Peters, Anju T. organization: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 12 givenname: Leslie C. surname: Grammer fullname: Grammer, Leslie C. organization: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 13 givenname: Kathleen E. surname: Harris fullname: Harris, Kathleen E. organization: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 14 givenname: Roderick G. surname: Carter fullname: Carter, Roderick G. organization: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 15 givenname: Atsushi surname: Kato fullname: Kato, Atsushi organization: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill – sequence: 16 givenname: Robert P. surname: Schleimer fullname: Schleimer, Robert P. email: rpschleimer@northwestern.edu organization: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill |
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| Copyright | 2013 American Academy of Allergy, Asthma & Immunology American Academy of Allergy, Asthma & Immunology 2014 INIST-CNRS Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved. Copyright Elsevier Limited Apr 2013 2013 American Academy of Allergy, Asthma & Immunology 2013 |
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| Keywords | 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 |
| Language | English |
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| Snippet | Despite the high prevalence and morbidity of chronic rhinosinusitis (CRS), little is known about the mechanisms that underlie its pathogenesis. Recent studies... Background Despite the high prevalence and morbidity of chronic rhinosinusitis (CRS), little is known about the mechanisms that underlie its pathogenesis.... BACKGROUND: Despite the high prevalence and morbidity of chronic rhinosinusitis (CRS), little is known about the mechanisms that underlie its pathogenesis.... |
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| SubjectTerms | 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 |
| Title | Chronic rhinosinusitis with nasal polyps is characterized by B-cell inflammation and EBV-induced protein 2 expression |
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