OP0042 THE TRANSCRIPTOME OF PAIRED MINOR AND MAJOR SALIVARY GLAND TISSUE IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME: TWO OF A KIND?

Abstract

Background:In patients with primary Sjögren’s syndrome (pSS), both minor and major salivary glands are targets of the disease. Infiltration of salivary glands by immune cells is characteristic for pSS. However, significant inter- and intra-individual variation exists in the size and composition of the infiltrates. Potential differences between minor and major salivary glands in immune cell presence and inflammatory pathway activation are unclear. This knowledge is essential for clinical trial design and precision therapy.Objectives:To compare the transcriptome of paired labial and parotid salivary gland tissue of patients with pSS and non-SS sicca controls.Methods:Thirty-nine pSS patients and 20 age- and sex-matched non-SS sicca controls, who participated in a prospective diagnostic cohort[1], were included. All pSS patients fulfilled 2016 ACR-EULAR criteria. RNA was isolated from formalin-fixed, paraffin-embedded labial and parotid gland tissue sections from the same individuals. Complementary DNA libraries were prepared and sequenced. Biopsies with evidence of sclerosing chronic sialoadenitis or mucosa-associated lymphoid tissue lymphoma were excluded in the current analysis. For differential gene expression analysis, patients were subdivided in four categories: I) non-SS sicca without lymphocytic infiltration, II) non-SS sicca with aspecific infiltration, III) pSS with negative biopsy (focus score<1), IV) pSS with positive biopsy (focus score≥1). For each differentially expressed gene (DEG), a false detection rate (FDR) was calculated. FDR<0.05 was considered significant.Results:Principal component analysis (PCA) showed that only pSS patients with a positive biopsy (group IV) could be separated from the non-SS sicca patients based on gene expression. When comparing the labial and parotid gland transcriptome, resp. 798 and 1461 DEGs (FDR-adjusted p-value<0.05, log2 fold change >1) were identified between groups I and IV. The top differentially regulated genes were mostly related to T and B cells.CXCL13, CCR6, MS4A1(CD20), FCRL4andDAZLwere among the genes with the highest positive fold change in both glands of biopsy-positive pSS patients. Overall, there was a moderate to strong correlation between fold changes in labial and parotid glands (R2=0.58, p-value<0.0001). Between biopsy-negative and biopsy-positive pSS (groups III and IV), 226 and 962 DEGs were identified for labial and parotid gland tissue, respectively. Interestingly, we could not identify DEGs between biopsy-negative pSS (group III) and non-SS sicca patients (group I).Conclusion:The transcriptome of labial and parotid gland tissue from pSS patients with a positive biopsy is overall comparable, while salivary gland tissue from biopsy-negative pSS patients shows a comparable gene expression profile to non-SS sicca controls. These results indicate that different treatment strategies may be necessary for biopsy-negative and biopsy-positive pSS patients.