Immunologic response of the laryngeal mucosa to extraesophageal reflux.
OBJECTIVE
Extraesophageal reflux is common. The treatment costs are high, and there are associations with other diseases, including laryngeal cancer. Our studies of the mucosal immune response to this common inflammatory disease suggest an important role for the nonclassic antigen-presenting molecule CD1d in the response to inflammation. This study was performed to further explore the relationship between the CD1d-NKT cell-iGb3 axis and reflux.


METHODS
We carried out a prospective study of laryngeal biopsies from 12 patients with laryngopharyngeal reflux and 11 controls. Quantitative multiple-color immunofluorescence using antibodies for lymphocytes (CD3, CD161) and classic and nonclassic major histocompatibility complex (I, II, beta2m, CD1d) was performed, and univariate and multivariate analysis and co-localization measurements were applied.


RESULTS
Epithelial major histocompatibility complex class I and II expression was unchanged by reflux, but expression of CD1d increased (p < 0.05; luminal layers) and confidence intervals diminished in the reflux group. Co-localization of NKT cells with CD1d increased in patients (p < 0.01); iGb3 exhibited strong expression throughout all layers of the laryngeal epithelium.


CONCLUSIONS
These data indicate a role for the CD1d-NKT cell-iGb3 axis in response to extraesophageal reflux in humans. This represents a useful target for novel diagnostics and treatments for this common condition.
Birchall
Martin A
MA
Laryngeal Research Group University of Bristol, Bristol, United, Kingdom.
Bailey
Michael
M
Gutowska-Owsiak
Danuta
D
Johnston
Nikki
N
Inman
Charlotte F
CF
Stokes
Christopher R
CR
Postma
Gregory
G
Pazmany
Laszlo
L
Koufman
Jamie A
JA
Phillips
Anne
A
Rees
Louisa E
LE
D000328:Adult; D055610:Antigens, CD1d / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D005764:Gastroesophageal Reflux / Q000276:immunology*; D005915:Globosides / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D007820:Laryngeal Mucosa / Q000276:immunology* / Q000378:metabolism*; D007830:Larynx / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D011446:Prospective Studies; D014281:Trihexosylceramides / Q000378:metabolism
D055610:Antigens, CD1d; C526877:CD1D protein, human; D005915:Globosides; D006649:Histocompatibility Antigens; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D014281:Trihexosylceramides; C514781:isoglobotrihexosylceramide