Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjögren's Syndrome.

Akinsola Oyelakin,Donald U Stone,Jill M Kramer,Christopher J Lessard,Satrajit Sinha,Scott S De Rossi,Lida Radfar,Erich Horeth,A Darise Farris,Monika Che,R Hal Scofield,David M Lewis,Astrid Rasmussen,Brandon Marzullo,Kiely Grundahl,Kathy L Sivils,Sang‐Won Min ,Zoya B Kurago ,Eun Kyeung Song ,Rose Anne Romano

doi:10.3389/fimmu.2020.606268

Abstract

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized primarily by immune-mediated destruction of exocrine tissues, such as those of the salivary and lacrimal glands, resulting in the loss of saliva and tear production, respectively. This disease predominantly affects middle-aged women, often in an insidious manner with the accumulation of subtle changes in glandular function occurring over many years. Patients commonly suffer from pSS symptoms for years before receiving a diagnosis. Currently, there is no effective cure for pSS and treatment options and targeted therapy approaches are limited due to a lack of our overall understanding of the disease etiology and its underlying pathology. To better elucidate the underlying molecular nature of this disease, we have performed RNA-sequencing to generate a comprehensive global gene expression profile of minor salivary glands from an ethnically diverse cohort of patients with pSS. Gene expression analysis has identified a number of pathways and networks that are relevant in pSS pathogenesis. Moreover, our detailed integrative analysis has revealed a primary Sjögren’s syndrome molecular signature that may represent important players acting as potential drivers of this disease. Finally, we have established that the global transcriptomic changes in pSS are likely to be attributed not only to various immune cell types within the salivary gland but also epithelial cells which are likely playing a contributing role. Overall, our comprehensive studies provide a database-enriched framework and resource for the identification and examination of key pathways, mediators, and new biomarkers important in the pathogenesis of this disease with the long-term goals of facilitating earlier diagnosis of pSS and to mitigate or abrogate the progression of this debilitating disease.

Highlights

Sjögren’s syndrome (SS) is a chronic, inflammatory autoimmune disease typically characterized by focal lymphocytic infiltration of exocrine glands that predominantly affect the salivary and lacrimal glands, resulting in oral and ocular dryness, respectively
RNA-Sequencing, Differentially Expressed Gene (DEG), Ingenuity Pathway Analysis (IPA), and Enrichment Analyses cDNA libraries were prepared using the TrueSeq RNA Sample Preparation Kit (Illumina) from RNA samples isolated from eight non-SS controls and nine Primary Sjögren’s syndrome (pSS) patients obtained from the OMRF
While the underlying molecular mechanisms driving the pathogenesis of SS has been an area of extensive research over the last several decades, very few advancements have been made in treating this disease

Summary

INTRODUCTION

Sjögren’s syndrome (SS) is a chronic, inflammatory autoimmune disease typically characterized by focal lymphocytic infiltration of exocrine glands that predominantly affect the salivary and lacrimal glands, resulting in oral and ocular dryness, respectively While this disease preferentially involves salivary and lacrimal glands, systemic effects are observed. Our comprehensive studies have re-affirmed the importance of key signaling molecules and pathways, but have identified novel genes and important cellular subtypes This knowledge can be mined for effective diagnosis and monitoring of pSS pathology with the long-term goal of developing targeted therapeutic strategies to better treat this chronic debilitating disease

MATERIALS AND METHODS

G Protein-Coupled Chemoattractant Receptor Activity

DISCUSSION

D Neuroinflammation Network

ETHICS STATEMENT