Sage Journals: Discover world-class research

Abstract

Background

Acute invasive fungal sinusitis (AIFS) is an aggressive and dangerous disease of the paranasal sinuses with high morbidity and mortality. The immune response at the level of the nasal mucosa, the site of entry, has not been previously evaluated.

Objective

To evaluate differential gene expression in the sinonasal mucosa of AIFS patients as compared to control patients using RNA sequencing.

Methods

Sinonasal tissue samples were prospectively obtained from consenting patients undergoing surgery between November, 2020 and November, 2021. RNA extraction and sequencing were performed and differential expression was analyzed to detect transcriptional differences between patient groups.

Results

Tissue samples were collected from 4 patients with active AIFS diagnoses, 2 patients with recovered AIFS, 1 patient with a diagnosis of non-invasive fungal ball, and 4 healthy controls. 255 genes were differentially expressed in AIFS patients as compared to control patients. Specific Gene Ontology (GO) biological processes that were identified as differentially expressed in AIFS patients as compared to controls included the following: 1. GO:0007155 (cell adhesion), 2. GO:0030199 (collagen fibril organization) and 3. GO:0001525 (angiogenesis).

Conclusion

Transcriptional differences were noted between AIFS and control patients in sinonasal tissue samples. Future work is necessary to determine causes of the differential gene expressions between AIFS and control patients, specifically those who are immunosuppressed, or with preexisting non-invasive forms of fungal sinusitis, to guide treatment and prevention strategies.

Keywords

invasive fungal sinusitis fungal sinusitis chronic sinusitis transcriptomics RNA sequencing

Get full access to this article

View all access options for this article.

References

Turner

Soudry

Nayak

Hwang

. Survival outcomes in acute invasive fungal sinusitis: A systematic review and quantitative synthesis of published evidence. Laryngoscope. 2013;123(5):1112–1118.

Tyler

Lam

Marino

, et al. Revisiting the controversy: The role of fungi in chronic rhinosinusitis. Int Forum Allergy Rhinol. 2021;11(11):1577–1587.

Burnham

Magliocca

Pettitt-Schieber

, et al. Intermediate Invasive Fungal Sinusitis, a Distinct Entity From Acute Fulminant and Chronic Invasive Fungal Sinusitis. Ann Otol Rhinol Laryngol. 2021;131(9). https://doi.org/10.1177/00034894211052854

Ryan

Marple

Halderman

. Fungal sinusitis: A spectrum of disease. Int Forum Allergy Rhinol. 2021;11(5):935–937.

Ramakrishnan

Gonzalez

Cooper

, et al. RNA Sequencing and pathway analysis identify tumor necrosis factor alpha driven small proline-rich protein dysregulation in chronic rhinosinusitis. Am J Rhinol Allergy. 2017;31(5):283–288.

Chen

McCarthy

Ritchie

Robinson

Smyth

. edgeR: differential analysis of sequence read count data. User’s Guide. 2008.

Lou

Friedman

Shedden

Hankenson

Woolf

. GAGE: generally applicable gene set enrichment for pathway analysis. BMC Bioinformatics. 2009;10(161). doi:10.1186/1471-2105-10-161

Wandell

Miller

Rathor

, et al. A multi-institutional review of outcomes in biopsy-proven acute invasive fungal sinusitis. Int Forum Allergy Rhinol. 2018;8(12):1459–1468.

Shintani-Smith

Luong

Ramakrishnan

Tan

French

Kern

. Acute invasive fungal sinusitis: Epidemiology and outcomes in the United States. Int Forum Allergy Rhinol. 2022;12(2):233–236.

10.

Melancon

Lindsey

Russell

Clinger

. The role of galactomannan Aspergillus antigen in diagnosing acute invasive fungal sinusitis. Int Forum Allergy Rhinol. 2019;9(1):60–66.

11.

Ribatti

Crivellato

. Immune cells and angiogenesis. J Cell Mol Med. 2009;13(9a):2822–2833.

12.

Byrd

O’Brien

Johnson

Lavigne

Reichner

. An extracellular matrix-based mechanism of rapid neutrophil extracellular trap formation in response to Candida albicans. J Immunol. 2013;190(8):4136–4148.

13.

Drummond

Gaffen

Hise

Brown

. Innate Defense against Fungal Pathogens. Cold Spring Harb Perspect Med. 2014;5(6).

14.

Glocker

Hennigs

Nabavi

, et al. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N Engl J Med. 2009;361(18):1727–1735.

15.

Viehl

Frey

Phommaly

, et al. Generation of mammaglobin-A-specific CD4 T cells and identification of candidate CD4 epitopes for breast cancer vaccine strategies. Breast Cancer Res Treat. 2008;109(2):305–314.

16.

Yang

Zhang

Wei

, et al. Single-Cell RNA Sequencing Reveals the Heterogeneity of Tumor-Associated Macrophage in Non-Small Cell Lung Cancer and Differences Between Sexes. Front Immunol. 2021;12(756722).

17.

Davis

Stucke

Khorki

, et al. Eosinophilic esophagitis–linked calpain 14 is an IL-13–induced protease that mediates esophageal epithelial barrier impairment. JCI Insight. 2016;1(4).

18.

Racevskis

Dill

Sparano

Ruan

. Molecular cloning of LMO41, a new human LIM domain gene. Biochim Biophys Acta. 1999;1445(1):148–153.

19.

Sum

EYM

O’Reilly

Jonas

Lindeman

Visvader

. The LIM domain protein Lmo4 is highly expressed in proliferating mouse epithelial tissues. J Histochem Cytochem. 2005;53(4):475–486.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

1.50 MB

2.02 MB