Immunologic Response of the Laryngeal Mucosa to Extraesophageal Reflux

Abstract

Objectives:

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, β2m, 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.

Keywords

CD1d extraesophageal reflux iGb3 NKT cell

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References

Gillett

Rees

Cogan

Birchall

Bailey

. Characterisation of the bacterial flora of the larynx [Abstract]. Clin Otolaryngol 2006;31:583.

Barker

Haverson

Stokes

Birchall

Bailey

. The larynx as an immunological organ: Immunological architecture in the pig as a large animal model. Clin Exp Immunol 2006;143:6–14.

Rees

Ayoub

Haverson

Birchall

Bailey

. Differential major histocompatibility complex class II locus expression on human laryngeal epithelium. Clin Exp Immunol 2003;134:497–502.

Rees

Jones

Ayoub

. Smoking influences the immunological architecture of the human larynx. Clin Immunol 2006;118:342–7.

Fontana

Pantaleo

Lavorini

Mutolo

Polli

Pistolesi

. Coughing in laryngectomized patients. Am J Respir Crit Care Med 1999;160:1578–84.

Koufman

Amin

Panetti

. Prevalence of reflux in 113 consecutive patients with laryngeal and voice disorders. Otolaryngol Head Neck Surg 2000;123:385–8. [Erratum in Otolaryngol Head Neck Surg 2001;124:104.]

Vaezi

Qadeer

Lopez

Colabianchi

. Laryngeal cancer and gastroesophageal reflux disease: A case-control study. Am J Med 2006;119:768–76.

Johnston

Dettmar

Lively

. Effect of pepsin on laryngeal stress protein (Sep70, Sep53, and Hsp70) response: Role in laryngopharyngeal reflux disease. Ann Otol Rhinol Laryngol 2006;115:47–58.

Rees

LEN

Pazmany

Gutowska-Owsiak

. The mucosal immune response to laryngopharyngeal reflux. Am J Respir Crit Care Med 2008;177:1187–93.

10.

Hobbs

Rees

LEN

Heyderman

Birchall

Bailey

. Major histocompatibility complex class I expression in human tonsillar and laryngeal epithelium. Clin Exp Immunol 2006;145:365–71.

11.

Inman

Rees

Barker

Haverson

Stokes

Bailey

. Validation of computer-assisted, pixel-based analysis of multiple-colour immunofluorescence histology. J Immunol Methods 2005;302:156–67.

12.

Zhou

Mattner

Cantu

III . Lysosomal glycosphingolipid recognition by NKT cells. Science 2004;306:1786–9.

13.

Mattner

Debord

Ismail

. Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 2005;434:525–9.