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The mucosal immune response to laryngopharyngeal reflux. Am J Respir Crit Care Med 2008 Jun 01;177(11):1187-93



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Pubmed Central ID




Scopus ID

2-s2.0-44449125150   26 Citations


RATIONALE: Laryngopharyngeal reflux (LPR) affects up to 20% of Western populations. Although individual morbidity is usually moderate, treatment costs are high and there are associations with other diseases, including laryngeal cancer. To date, there have been no studies of the mucosal immune response to this common inflammatory disease.

OBJECTIVES: To determine the mucosal immune response to LPR.

METHODS: We performed a prospective immunologic study of laryngeal biopsies from patients with LPR and control subjects (n = 12 and 11, respectively), and of primary laryngeal epithelial cells in vitro.

MEASUREMENTS AND MAIN RESULTS: Quantitative multiple-color immunofluorescence, using antibodies for lymphocytes (CD4, CD8, CD3, CD79, CD161), granulocytes (CD68, EMBP), monocytic cells (CD68, major histocompatibility complex [MHC] class II), and classical and nonclassical MHC (I, II, beta(2)-microglobulin, CD1d). Univariate and multivariate analysis and colocalization measurements were applied. There was an increase in percentage area of mucosal CD8(+) cells in the epithelium (P < 0.005), whereas other leukocyte and granulocyte antigens were unchanged. Although epithelial MHC class I and II expression was unchanged by reflux, expression of the nonclassical MHC molecule CD1d increased (P < 0.05, luminal layers). In vitro, laryngeal epithelial cells constitutively expressed CD1d. CD1d and MHC I expression were inversely related in all subjects, in a pattern which appears to be unique to the upper airway. Colocalization of natural killer T (NKT) cells with CD1d increased in patients (P < 0.01).

CONCLUSIONS: These data indicate a role for the CD1d-NKT cell axis in response to LPR in humans. This represents a useful target for novel diagnostics and treatments in this common condition.

Author List

Rees LE, Pazmany L, Gutowska-Owsiak D, Inman CF, Phillips A, Stokes CR, Johnston N, Koufman JA, Postma G, Bailey M, Birchall MA


Nikki Johnston PhD Associate Professor in the Otolaryngology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antigen-Presenting Cells
Antigens, CD
Case-Control Studies
Epithelial Cells
Gastroesophageal Reflux
Immunity, Mucosal
Laryngeal Mucosa
Middle Aged
Prospective Studies
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280