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Diversity of IgE-encoding transcripts in sinus mucosa of subjects diagnosed with non-allergic fungal eosinophilic sinusitis

Levin, Mattias LU ; Lor Wai, Tan ; Baker, Leonie ; Wormald, Peter-John ; Greiff, Lennart LU and Ohlin, Mats LU orcid (2011) In Clinical and Experimental Allergy 41(6). p.811-820
Abstract
Abstract in Undetermined
Background The role of allergy in the aetiopathogenesis of chronic rhinosinusitis (CRS) remains controversial. For example, in some cases with sinus fungal infections allergy can be demonstrated by standard tests. In other cases, such signs can be absent despite elevated levels of IgE-positive cells in sinus tissue and the presence of IgE and eosinophils in the sinus mucous. Objective To define the nature of molecular diversity in antibodies of the IgE isotype at the site of local inflammation in subjects diagnosed with non-allergic fungal eosinophilic sinusitis (NAFES). Methods The local occurrence and sequence characteristics of IgE-encoding transcripts in NAFES patients were investigated and compared with... (More)
Abstract in Undetermined
Background The role of allergy in the aetiopathogenesis of chronic rhinosinusitis (CRS) remains controversial. For example, in some cases with sinus fungal infections allergy can be demonstrated by standard tests. In other cases, such signs can be absent despite elevated levels of IgE-positive cells in sinus tissue and the presence of IgE and eosinophils in the sinus mucous. Objective To define the nature of molecular diversity in antibodies of the IgE isotype at the site of local inflammation in subjects diagnosed with non-allergic fungal eosinophilic sinusitis (NAFES). Methods The local occurrence and sequence characteristics of IgE-encoding transcripts in NAFES patients were investigated and compared with sequences found in subjects diagnosed with CRS featuring systemic allergy. These sequences have also been compared with other reported IgE-encoding transcriptomes. Results IGHV genes derived from major subgroups 1, 3, 4 and 5 and a diverse set of IGHD and IGHJ genes were shown to create the IgE repertoire in patients diagnosed with NAFES and CRS. The average lengths of the third hypervariable loop in these populations were 15.8 and 14.6 residues. The sequences showed evidence of extensive somatic hypermutation (mutation frequency: NAFES, 6.4±3.2%; CRS, 7.0±4.4%) with substitutions targeted to complementarity-determining regions. These sequence collections thus show extensive similarities to those found in other polyclonal Ig repertoires including those encoding IgE. Conclusion and Clinical Relevance We conclude that sinus IgE-encoding transcripts in subjects diagnosed with NAFES show evidence of conventional IgE responses and we suggest that allergens with characteristics of classical antigens should be investigated for a role in the local response occurring in NAFES. This investigation illustrates that assessment of local immunity might be an important diagnostic tool in conditions like NAFES with no systemic signs of allergy to identify or rule out an allergic component of the patient's disease. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical and Experimental Allergy
volume
41
issue
6
pages
811 - 820
publisher
Wiley
external identifiers
  • wos:000290489800009
  • scopus:79955751727
  • pmid:21561493
ISSN
1365-2222
DOI
10.1111/j.1365-2222.2011.03724.x
project
Human IgE repertoires and an anti-allergome resource
language
English
LU publication?
yes
id
2efbe3ff-d033-4301-a395-571cd122b3eb (old id 1764853)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21561493?dopt=Abstract
date added to LUP
2016-04-04 07:13:48
date last changed
2022-01-29 01:55:04
@article{2efbe3ff-d033-4301-a395-571cd122b3eb,
  abstract     = {{Abstract in Undetermined<br/>Background The role of allergy in the aetiopathogenesis of chronic rhinosinusitis (CRS) remains controversial. For example, in some cases with sinus fungal infections allergy can be demonstrated by standard tests. In other cases, such signs can be absent despite elevated levels of IgE-positive cells in sinus tissue and the presence of IgE and eosinophils in the sinus mucous. Objective To define the nature of molecular diversity in antibodies of the IgE isotype at the site of local inflammation in subjects diagnosed with non-allergic fungal eosinophilic sinusitis (NAFES). Methods The local occurrence and sequence characteristics of IgE-encoding transcripts in NAFES patients were investigated and compared with sequences found in subjects diagnosed with CRS featuring systemic allergy. These sequences have also been compared with other reported IgE-encoding transcriptomes. Results IGHV genes derived from major subgroups 1, 3, 4 and 5 and a diverse set of IGHD and IGHJ genes were shown to create the IgE repertoire in patients diagnosed with NAFES and CRS. The average lengths of the third hypervariable loop in these populations were 15.8 and 14.6 residues. The sequences showed evidence of extensive somatic hypermutation (mutation frequency: NAFES, 6.4±3.2%; CRS, 7.0±4.4%) with substitutions targeted to complementarity-determining regions. These sequence collections thus show extensive similarities to those found in other polyclonal Ig repertoires including those encoding IgE. Conclusion and Clinical Relevance We conclude that sinus IgE-encoding transcripts in subjects diagnosed with NAFES show evidence of conventional IgE responses and we suggest that allergens with characteristics of classical antigens should be investigated for a role in the local response occurring in NAFES. This investigation illustrates that assessment of local immunity might be an important diagnostic tool in conditions like NAFES with no systemic signs of allergy to identify or rule out an allergic component of the patient's disease.}},
  author       = {{Levin, Mattias and Lor Wai, Tan and Baker, Leonie and Wormald, Peter-John and Greiff, Lennart and Ohlin, Mats}},
  issn         = {{1365-2222}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{811--820}},
  publisher    = {{Wiley}},
  series       = {{Clinical and Experimental Allergy}},
  title        = {{Diversity of IgE-encoding transcripts in sinus mucosa of subjects diagnosed with non-allergic fungal eosinophilic sinusitis}},
  url          = {{http://dx.doi.org/10.1111/j.1365-2222.2011.03724.x}},
  doi          = {{10.1111/j.1365-2222.2011.03724.x}},
  volume       = {{41}},
  year         = {{2011}},
}