Sjogren's Syndrome Minor Salivary Gland CD4+ T Cells Associate with Oral Disease Features and Have a T Follicular Helper-like Transcriptional Profile

Michelle L. Joachims¹, Kerry M. Leehan¹, Mikhail Dozmorov^1,2, Zijian Pan¹, Astrid Rasmussen¹, Lida Radfar³, David M. Lewis⁴, Donald U. Stone^5,6, Kiely Grundahl⁷, R. Hal Scofield^1,8,9, Christopher J. Lessard¹, Jonathan Wren¹, Linda F. Thompson¹, Kathy L. Sivils¹⁰, Jacen Maier-Moore^1,11 and A. Darise Farris¹, ¹Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, ²Biostatistics, Virginia Commonwealth University, Richmond, VA, ³Department of Oral Diagnosis and Radiology, University of Oklahoma College of Dentistry, Oklahoma City, OK, ⁴Department of Oral and Maxillofacial Pathology, University of Oklahoma College of Dentistry, Oklahoma City, OK, ⁵Ophthalmology, Johns Hopkins University, Baltimore, MD, ⁶King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia, ⁷Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma CIty, OK, ⁸Department of Veterans Affairs Medical Center, Oklahoma City, OK, ⁹Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, ¹⁰Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma, OK, ¹¹Clinical Laboratory Science, University of Texas at El Paso, El Paso, TX

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: CD T cells, Sjogren's syndrome and salivary gland

Session Information

Date: Tuesday, October 23, 2018

Title: 5T092 ACR Abstract: T Cell Biology & Targets in Autoimmune & Inflammatory Disease (2797–2801)

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.

Disclosure: M. L. Joachims, None; K. M. Leehan, None; M. Dozmorov, None; Z. Pan, None; A. Rasmussen, None; L. Radfar, None; D. M. Lewis, None; D. U. Stone, None; K. Grundahl, None; R. H. Scofield, NIH, ept Veran Affirs,Lupus esearch Institute, 2,Dept of Veterans Affairs, Universiy of Oklahoma, 3,Boston Pharmacueticals, 5; C. J. Lessard, None; J. Wren, None; L. F. Thompson, None; K. L. Sivils, None; J. Maier-Moore, None; A. D. Farris, None.

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 9). 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 .

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