Sclerosing Sialadenitis Is Associated With Salivary Gland Hypofunction and a Unique Gene Expression Profile in Sjögren's Syndrome
Hongen Yin, Thomas J F Pranzatelli, Benjamin N French, Nan Zhang, Blake M Warner, John A Chiorini, NIDCD/NIDCR Genomics and Computational Biology Core, Hongen Yin, Thomas J F Pranzatelli, Benjamin N French, Nan Zhang, Blake M Warner, John A Chiorini, NIDCD/NIDCR Genomics and Computational Biology Core
Abstract
Purpose: To develop a novel method to quantify the amount of fibrosis in the salivary gland and to investigate the relationship between fibrosis and specific symptoms associated with Sjögren's syndrome (SS) using this method.
Materials and methods: Paraffin-embedded labial salivary gland (LSG) slides from 20 female SS patients and their clinical and LSG pathology data were obtained from the Sjögren's International Collaborative Clinical Alliance. Relative interstitial fibrosis area (RIFA) in Masson's trichrome-stained LSG sections was quantified from digitally scanned slides and used for correlation analysis. Gene expression levels were assessed by microarray analysis. Core promoter accessibility for RIFA-correlated genes was determined using DNase I hypersensitive sites sequencing analysis.
Results: RIFA was significantly correlated with unstimulated whole saliva flow rate in SS patients. Sixteen genes were significantly and positively correlated with RIFA. In a separate analysis, a group of differentially expressed genes was identified by comparing severe and moderate fibrosis groups. This combined set of genes was distinct from differentially expressed genes identified in lung epithelium from idiopathic pulmonary fibrosis patients compared with controls. Single-cell RNA sequencing analysis of salivary glands suggested most of the RIFA-correlated genes are expressed by fibroblasts in the gland and are in a permissive chromatin state.
Conclusion: RIFA quantification is a novel method for assessing interstitial fibrosis and the impact of fibrosis on SS symptoms. Loss of gland function may be associated with salivary gland fibrosis, which is likely to be driven by a unique set of genes that are mainly expressed by fibroblasts.
Trial registration: ClinicalTrials.gov NCT02327884.
Keywords: Sjögren’s syndrome; salivary gland hypofunction; salivary gland interstitial fibrosis; sclerosing sialadenitis; transcriptomic gene expression profile.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Copyright © 2021 Yin, Pranzatelli, French, Zhang, Warner, Chiorini and NIDCD/NIDCR Genomics and Computational Biology Core.
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