Evidence for altered levels of IgD in the nasal airway mucosa of patients with chronic rhinosinusitis

Jin Young Min, Jayakar V. Nayak, Kathryn E Hulse, Whitney Stevens, Paul A. Raju, Julia H. Huang, Lydia A. Suh, Griet A. Van Roey, James E. Norton, Roderick G. Carter, Caroline P.E. Price, Ava R. Weibman, Ali R. Rashan, Eliver E. Ghosn, Zara M. Patel, Tetsuya Homma, David B Conley Jr, Kevin Christian Welch, Stephanie Shintani Smith, Anju Tripathi Peters & 8 others Leslie C Grammer III, Kathleen E. Harris, Atsushi Kato, Peter H. Hwang, Robert C Kern, Leonore A. Herzenberg, Robert P Schleimer, Bruce Kuang-Huay Tan*

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background IgD is an enigmatic antibody isotype best known when coexpressed with IgM on naive B cells. However, increased soluble IgD (sIgD) levels and increased IgD+IgM B-cell populations have been described in the human upper respiratory mucosa. Objective We assessed whether levels of sIgD and IgD+ B cell counts are altered in nasal tissue from patients with chronic rhinosinusitis (CRS). We further characterized IgD+ B-cell populations and explored clinical and local inflammatory factors associated with tissue sIgD levels. Methods sIgD levels were measured by means of ELISA in nasal tissues, nasal lavage fluid, sera, and supernatants of dissociated nasal tissues. IgD+ cells were identified by using immunofluorescence and flow cytometry. Inflammatory mediator levels in tissues were assessed by using real-time PCR and multiplex immunoassays. Bacterial cultures from the middle meatus were performed. Underlying medical history and medicine use were obtained from medical records. Results sIgD levels and numbers of IgD+ cells were significantly increased in uncinate tissue (UT) of patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared with that of control subjects (4-fold, P <.05). IgD+ cells were densely scattered in the periglandular regions of UT from patients with CRSsNP. We also found that IgD+CD19+CD38bright plasmablast numbers were significantly increased in tissues from patients with CRSsNP compared with control tissues (P <.05). Among numerous factors tested, IL-2 levels were increased in UT from patients with CRSsNP and were positively correlated with tissue IgD levels. Additionally, supernatants of IL-2–stimulated dissociated tissue from patients with CRSsNP had significantly increased sIgD levels compared with those in IL-2–stimulated dissociated control tissue ex vivo (P <.05). Tissue from patients with CRS with preoperative antibiotic use or those with pathogenic bacteria showed higher IgD levels compared with tissue from patients without these variables (P <.05). Conclusion sIgD levels and IgD+CD19+CD38bright plasmablast counts were increased in nasal tissue of patients with CRSsNP. IgD levels were associated with increased IL-2 levels and the presence of pathogenic bacteria. These findings suggest that IgD might contribute to enhancement mucosal immunity or inflammation or respond to bacterial infections in patients with CRS, especially CRSsNP.

Original languageEnglish (US)
Pages (from-to)1562-1571.e5
JournalJournal of Allergy and Clinical Immunology
Volume140
Issue number6
DOIs
StatePublished - Dec 1 2017

Fingerprint

Immunoglobulin D
Nasal Mucosa
Nasal Polyps
Nose
B-Lymphocytes
Interleukin-2
Immunoglobulin M
Cell Count
Nasal Lavage Fluid
Bacteria
History of Medicine

Keywords

  • B cells
  • Chronic rhinosinusitis
  • IL-2
  • IgD
  • bacterial infection
  • mucosal immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Min, Jin Young ; Nayak, Jayakar V. ; Hulse, Kathryn E ; Stevens, Whitney ; Raju, Paul A. ; Huang, Julia H. ; Suh, Lydia A. ; Van Roey, Griet A. ; Norton, James E. ; Carter, Roderick G. ; Price, Caroline P.E. ; Weibman, Ava R. ; Rashan, Ali R. ; Ghosn, Eliver E. ; Patel, Zara M. ; Homma, Tetsuya ; Conley Jr, David B ; Welch, Kevin Christian ; Smith, Stephanie Shintani ; Peters, Anju Tripathi ; Grammer III, Leslie C ; Harris, Kathleen E. ; Kato, Atsushi ; Hwang, Peter H. ; Kern, Robert C ; Herzenberg, Leonore A. ; Schleimer, Robert P ; Tan, Bruce Kuang-Huay. / Evidence for altered levels of IgD in the nasal airway mucosa of patients with chronic rhinosinusitis. In: Journal of Allergy and Clinical Immunology. 2017 ; Vol. 140, No. 6. pp. 1562-1571.e5.
@article{60aa71c8552549409082f7e94a6df62a,
title = "Evidence for altered levels of IgD in the nasal airway mucosa of patients with chronic rhinosinusitis",
abstract = "Background IgD is an enigmatic antibody isotype best known when coexpressed with IgM on naive B cells. However, increased soluble IgD (sIgD) levels and increased IgD+IgM− B-cell populations have been described in the human upper respiratory mucosa. Objective We assessed whether levels of sIgD and IgD+ B cell counts are altered in nasal tissue from patients with chronic rhinosinusitis (CRS). We further characterized IgD+ B-cell populations and explored clinical and local inflammatory factors associated with tissue sIgD levels. Methods sIgD levels were measured by means of ELISA in nasal tissues, nasal lavage fluid, sera, and supernatants of dissociated nasal tissues. IgD+ cells were identified by using immunofluorescence and flow cytometry. Inflammatory mediator levels in tissues were assessed by using real-time PCR and multiplex immunoassays. Bacterial cultures from the middle meatus were performed. Underlying medical history and medicine use were obtained from medical records. Results sIgD levels and numbers of IgD+ cells were significantly increased in uncinate tissue (UT) of patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared with that of control subjects (4-fold, P <.05). IgD+ cells were densely scattered in the periglandular regions of UT from patients with CRSsNP. We also found that IgD+CD19+CD38bright plasmablast numbers were significantly increased in tissues from patients with CRSsNP compared with control tissues (P <.05). Among numerous factors tested, IL-2 levels were increased in UT from patients with CRSsNP and were positively correlated with tissue IgD levels. Additionally, supernatants of IL-2–stimulated dissociated tissue from patients with CRSsNP had significantly increased sIgD levels compared with those in IL-2–stimulated dissociated control tissue ex vivo (P <.05). Tissue from patients with CRS with preoperative antibiotic use or those with pathogenic bacteria showed higher IgD levels compared with tissue from patients without these variables (P <.05). Conclusion sIgD levels and IgD+CD19+CD38bright plasmablast counts were increased in nasal tissue of patients with CRSsNP. IgD levels were associated with increased IL-2 levels and the presence of pathogenic bacteria. These findings suggest that IgD might contribute to enhancement mucosal immunity or inflammation or respond to bacterial infections in patients with CRS, especially CRSsNP.",
keywords = "B cells, Chronic rhinosinusitis, IL-2, IgD, bacterial infection, mucosal immunity",
author = "Min, {Jin Young} and Nayak, {Jayakar V.} and Hulse, {Kathryn E} and Whitney Stevens and Raju, {Paul A.} and Huang, {Julia H.} and Suh, {Lydia A.} and {Van Roey}, {Griet A.} and Norton, {James E.} and Carter, {Roderick G.} and Price, {Caroline P.E.} and Weibman, {Ava R.} and Rashan, {Ali R.} and Ghosn, {Eliver E.} and Patel, {Zara M.} and Tetsuya Homma and {Conley Jr}, {David B} and Welch, {Kevin Christian} and Smith, {Stephanie Shintani} and Peters, {Anju Tripathi} and {Grammer III}, {Leslie C} and Harris, {Kathleen E.} and Atsushi Kato and Hwang, {Peter H.} and Kern, {Robert C} and Herzenberg, {Leonore A.} and Schleimer, {Robert P} and Tan, {Bruce Kuang-Huay}",
year = "2017",
month = "12",
day = "1",
doi = "10.1016/j.jaci.2017.05.032",
language = "English (US)",
volume = "140",
pages = "1562--1571.e5",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "6",

}

Min, JY, Nayak, JV, Hulse, KE, Stevens, W, Raju, PA, Huang, JH, Suh, LA, Van Roey, GA, Norton, JE, Carter, RG, Price, CPE, Weibman, AR, Rashan, AR, Ghosn, EE, Patel, ZM, Homma, T, Conley Jr, DB, Welch, KC, Smith, SS, Peters, AT, Grammer III, LC, Harris, KE, Kato, A, Hwang, PH, Kern, RC, Herzenberg, LA, Schleimer, RP & Tan, BK-H 2017, 'Evidence for altered levels of IgD in the nasal airway mucosa of patients with chronic rhinosinusitis', Journal of Allergy and Clinical Immunology, vol. 140, no. 6, pp. 1562-1571.e5. https://doi.org/10.1016/j.jaci.2017.05.032

Evidence for altered levels of IgD in the nasal airway mucosa of patients with chronic rhinosinusitis. / Min, Jin Young; Nayak, Jayakar V.; Hulse, Kathryn E; Stevens, Whitney; Raju, Paul A.; Huang, Julia H.; Suh, Lydia A.; Van Roey, Griet A.; Norton, James E.; Carter, Roderick G.; Price, Caroline P.E.; Weibman, Ava R.; Rashan, Ali R.; Ghosn, Eliver E.; Patel, Zara M.; Homma, Tetsuya; Conley Jr, David B; Welch, Kevin Christian; Smith, Stephanie Shintani; Peters, Anju Tripathi; Grammer III, Leslie C; Harris, Kathleen E.; Kato, Atsushi; Hwang, Peter H.; Kern, Robert C; Herzenberg, Leonore A.; Schleimer, Robert P; Tan, Bruce Kuang-Huay.

In: Journal of Allergy and Clinical Immunology, Vol. 140, No. 6, 01.12.2017, p. 1562-1571.e5.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evidence for altered levels of IgD in the nasal airway mucosa of patients with chronic rhinosinusitis

AU - Min, Jin Young

AU - Nayak, Jayakar V.

AU - Hulse, Kathryn E

AU - Stevens, Whitney

AU - Raju, Paul A.

AU - Huang, Julia H.

AU - Suh, Lydia A.

AU - Van Roey, Griet A.

AU - Norton, James E.

AU - Carter, Roderick G.

AU - Price, Caroline P.E.

AU - Weibman, Ava R.

AU - Rashan, Ali R.

AU - Ghosn, Eliver E.

AU - Patel, Zara M.

AU - Homma, Tetsuya

AU - Conley Jr, David B

AU - Welch, Kevin Christian

AU - Smith, Stephanie Shintani

AU - Peters, Anju Tripathi

AU - Grammer III, Leslie C

AU - Harris, Kathleen E.

AU - Kato, Atsushi

AU - Hwang, Peter H.

AU - Kern, Robert C

AU - Herzenberg, Leonore A.

AU - Schleimer, Robert P

AU - Tan, Bruce Kuang-Huay

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Background IgD is an enigmatic antibody isotype best known when coexpressed with IgM on naive B cells. However, increased soluble IgD (sIgD) levels and increased IgD+IgM− B-cell populations have been described in the human upper respiratory mucosa. Objective We assessed whether levels of sIgD and IgD+ B cell counts are altered in nasal tissue from patients with chronic rhinosinusitis (CRS). We further characterized IgD+ B-cell populations and explored clinical and local inflammatory factors associated with tissue sIgD levels. Methods sIgD levels were measured by means of ELISA in nasal tissues, nasal lavage fluid, sera, and supernatants of dissociated nasal tissues. IgD+ cells were identified by using immunofluorescence and flow cytometry. Inflammatory mediator levels in tissues were assessed by using real-time PCR and multiplex immunoassays. Bacterial cultures from the middle meatus were performed. Underlying medical history and medicine use were obtained from medical records. Results sIgD levels and numbers of IgD+ cells were significantly increased in uncinate tissue (UT) of patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared with that of control subjects (4-fold, P <.05). IgD+ cells were densely scattered in the periglandular regions of UT from patients with CRSsNP. We also found that IgD+CD19+CD38bright plasmablast numbers were significantly increased in tissues from patients with CRSsNP compared with control tissues (P <.05). Among numerous factors tested, IL-2 levels were increased in UT from patients with CRSsNP and were positively correlated with tissue IgD levels. Additionally, supernatants of IL-2–stimulated dissociated tissue from patients with CRSsNP had significantly increased sIgD levels compared with those in IL-2–stimulated dissociated control tissue ex vivo (P <.05). Tissue from patients with CRS with preoperative antibiotic use or those with pathogenic bacteria showed higher IgD levels compared with tissue from patients without these variables (P <.05). Conclusion sIgD levels and IgD+CD19+CD38bright plasmablast counts were increased in nasal tissue of patients with CRSsNP. IgD levels were associated with increased IL-2 levels and the presence of pathogenic bacteria. These findings suggest that IgD might contribute to enhancement mucosal immunity or inflammation or respond to bacterial infections in patients with CRS, especially CRSsNP.

AB - Background IgD is an enigmatic antibody isotype best known when coexpressed with IgM on naive B cells. However, increased soluble IgD (sIgD) levels and increased IgD+IgM− B-cell populations have been described in the human upper respiratory mucosa. Objective We assessed whether levels of sIgD and IgD+ B cell counts are altered in nasal tissue from patients with chronic rhinosinusitis (CRS). We further characterized IgD+ B-cell populations and explored clinical and local inflammatory factors associated with tissue sIgD levels. Methods sIgD levels were measured by means of ELISA in nasal tissues, nasal lavage fluid, sera, and supernatants of dissociated nasal tissues. IgD+ cells were identified by using immunofluorescence and flow cytometry. Inflammatory mediator levels in tissues were assessed by using real-time PCR and multiplex immunoassays. Bacterial cultures from the middle meatus were performed. Underlying medical history and medicine use were obtained from medical records. Results sIgD levels and numbers of IgD+ cells were significantly increased in uncinate tissue (UT) of patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared with that of control subjects (4-fold, P <.05). IgD+ cells were densely scattered in the periglandular regions of UT from patients with CRSsNP. We also found that IgD+CD19+CD38bright plasmablast numbers were significantly increased in tissues from patients with CRSsNP compared with control tissues (P <.05). Among numerous factors tested, IL-2 levels were increased in UT from patients with CRSsNP and were positively correlated with tissue IgD levels. Additionally, supernatants of IL-2–stimulated dissociated tissue from patients with CRSsNP had significantly increased sIgD levels compared with those in IL-2–stimulated dissociated control tissue ex vivo (P <.05). Tissue from patients with CRS with preoperative antibiotic use or those with pathogenic bacteria showed higher IgD levels compared with tissue from patients without these variables (P <.05). Conclusion sIgD levels and IgD+CD19+CD38bright plasmablast counts were increased in nasal tissue of patients with CRSsNP. IgD levels were associated with increased IL-2 levels and the presence of pathogenic bacteria. These findings suggest that IgD might contribute to enhancement mucosal immunity or inflammation or respond to bacterial infections in patients with CRS, especially CRSsNP.

KW - B cells

KW - Chronic rhinosinusitis

KW - IL-2

KW - IgD

KW - bacterial infection

KW - mucosal immunity

UR - http://www.scopus.com/inward/record.url?scp=85025839455&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85025839455&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2017.05.032

DO - 10.1016/j.jaci.2017.05.032

M3 - Article

VL - 140

SP - 1562-1571.e5

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 6

ER -