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Expression of protease-activated receptors in allergic fungal rhinosinusitis

Authors

  • Charles S. Ebert Jr. MD, MPH,

    Corresponding author
    1. Department of Otolaryngology–Head and Neck Surgery, University of North Carolina–Chapel Hill, Chapel Hill, NC
    • Correspondence to: Charles S. Ebert, Jr., MD, MPH, University of North Carolina CB#7070, Department of Otolaryngology–Head and Neck Surgery, Division of Rhinology, Allergy, and Endoscopic Skull Base Surgery, Chapel Hill, NC 27599-7070; e-mail: cebert@med.unc.edu

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  • Kibwei A. McKinney MD,

    1. Department of Otolaryngology–Head and Neck Surgery, University of North Carolina–Chapel Hill, Chapel Hill, NC
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  • Gene Urrutia PhD,

    1. Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina–Chapel Hill, Chapel Hill, NC
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  • Michael Wu PhD,

    1. Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina–Chapel Hill, Chapel Hill, NC
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  • Austin S. Rose MD,

    1. Department of Otolaryngology–Head and Neck Surgery, University of North Carolina–Chapel Hill, Chapel Hill, NC
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  • Gita M. Fleischman MD,

    1. Department of Otolaryngology–Head and Neck Surgery, University of North Carolina–Chapel Hill, Chapel Hill, NC
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  • Brian Thorp MD,

    1. Department of Otolaryngology–Head and Neck Surgery, University of North Carolina–Chapel Hill, Chapel Hill, NC
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  • Brent A. Senior MD,

    1. Department of Otolaryngology–Head and Neck Surgery, University of North Carolina–Chapel Hill, Chapel Hill, NC
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  • Adam M. Zanation MD

    1. Department of Otolaryngology–Head and Neck Surgery, University of North Carolina–Chapel Hill, Chapel Hill, NC
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  • Potential conflict of interest: None provided.

Abstract

Background

The etiology of the intense inflammatory response showed by patients with allergic fungal rhinosinusitis (AFRS) remains a mystery. Potential sources of this inflammation may include fungal proteases. Protease-activated receptors (PARs) are components of the innate immune response that are modulated by proteolytic activity and are involved in potentiating T helper 2 (Th2) responses. The objective of the study was to determine whether there is differential expression of PARs in patients with AFRS compared to controls.

Methods

The study was designed as a comparison of gene expression profiles in patients with AFRS vs diseased and nondiseased controls. Twenty-five patients were enrolled. Patients with AFRS (n = 15) were compared to nondiseased controls (n = 5) undergoing minimally invasive pituitary surgery (MIPS) and patients with chronic rhinosinusitis with nasal polyps (CRSwNP, n = 5) undergoing functional endoscopic sinus surgery (FESS). Ethmoid mucosa RNA was hybridized to 4×44K microarray chips. Four gene probes (PAR1, PAR2, PAR3, and PAR4) were used to assess for differential expression. A linear-mixed model was used to account for some patients having multiple samples. Significance level was determined at p < 0.05.

Results

Of the 4 probes, only PAR3 showed statistically significant differential expression between AFRS and nondiseased control samples (p = 0.03) as well as a 2.21-fold change. No additional statistical difference in PAR expression among the comparison groups was noted.

Conclusion

PARs have been shown to enhance production of inflammatory cytokines and potentiate Th2 responses. In this initial report, patients with AFRS have a significantly increased expression of PAR3 compared to nondiseased controls.

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