Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: The predominant salivary gland (SG) T cell types contributing to disease in Sjögren’s syndrome (SS) are unclear. This study assessed the frequency and number of SG CD3+ T cell subtypes for association with SS disease features and compared the SG CD4+ T cell transcriptome of primary SS subjects to that of sicca controls not meeting criteria for SS.
Methods: CD3+ T cells from SG biopsy tissue of subjects with primary SS and non-SS sicca were evaluated for proportion (n=51 SS, n=69 non-SS) and number/mg biopsy tissue (n=34 SS, n=56 non-SS) of T cell subsets defined by CD3, CD4, CD8 and CD45RA using flow cytometry. Proportions of memory CD4+ T cells were evaluated for correlation with clinical and oral disease parameters. Sorted salivary gland memory CD4+ T cells from a subset of focus score positive SS cases (n=17) and focus score negative non-SS subjects (n=15) were evaluated for global gene expression by microarray. Differentially expressed genes were assessed using the limma R package, and bioinformatics analyses were performed using Ingenuity Pathways Analysis and Gene Set Enrichment Analysis.
Results: Proportions of CD4+CD45RA– T cells (mean ± SEM pSS: 33.2%±2.0, non-SS: 21.9%±1.2, p<0.0001) but not those of other CD3+ T cell subsets were increased in SS cases compared to non-SS sicca subjects. Proportions of SG CD4+ memory T cells positively correlated with SG focus score (r=0.47, p<0.0001), morphologic area of SG fibrosis (r=0.35, p=0.006), and van Bijsterveld corneal damage score (r=0.37, p<0.0001), with relationships remaining after age correction. Differentially expressed (DE) genes in SS cases versus non-SS sicca subjects were enriched for T follicular helper (Tfh), interferon, T cell homeostasis, resistance to apoptosis, atypical lymphoid trafficking and elevated inflammatory response pathways, but not Th17 profile. Predicted upstream drivers of the DE genes included CXCL13, CD40/CD40 ligand and Bcl6, while predicted decreased effects included FoxP3, Fas, STAT6 and mTOR.
Conclusion: Proportion and number of SG memory CD4+ T cells selectively associate with key SS disease features, and SG memory CD4+ T cells are enriched for a predominant Tfh-like cell profile.
To cite this abstract in AMA style:Joachims ML, Leehan KM, Dozmorov M, Pan Z, Rasmussen A, Radfar L, Lewis DM, Stone DU, Grundahl K, Scofield RH, Lessard CJ, Wren J, Thompson LF, Sivils KL, Maier-Moore J, Farris AD. Sjogren’s Syndrome Minor Salivary Gland CD4+ T Cells Associate with Oral Disease Features and Have a T Follicular Helper-like Transcriptional Profile [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/sjogrens-syndrome-minor-salivary-gland-cd4-t-cells-associate-with-oral-disease-features-and-have-a-t-follicular-helper-like-transcriptional-profile/. Accessed October 1, 2022.
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