Sjögren’s Syndrome Minor Salivary Gland CD4+ Memory T Cells Associate with Glandular Disease Features and Have a Germinal Center T Follicular Helper Transcriptional Profile
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Isolation of SG Memory CD4+ T Cells and cDNA Preparation
2.3. Flow Cytometry Analysis
2.4. Microarray Data Analysis
2.5. Salivary Gland Imaging
2.6. Other Statistical Analyses
3. Results
3.1. Memory CD4+ T Cells Are Increased in pSS SG
3.2. Numbers of SG CD4+ Antigen-Experienced T Cells Associate with Biopsy Focus Scores
3.3. Absolute Numbers of SG Antigen-Experienced T Cells Associate with the Extent of Salivary Gland Fibrosis
3.4. Proportions of SG CD4+ Memory T Cells Correlate with Clinical Features of SS
3.5. Characterization of the pSS CD4+CD45RA− SG T Cell Transcriptome
3.6. The Transcriptomes of pSS SG Memory CD4+ T Cells Include DEG for Homing, Interaction and Survival Functions
3.7. pSS SG Memory CD4+ T Cells Display a Germinal Center Tfh Cell Gene Signature
3.8. SG biopsies from pSS Subjects Showing SG Memory T Cell Tfh Gene Signatures Display Atypical Ectopic Lymphoid Structures
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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FACS Study | Microarray Study | |||||
---|---|---|---|---|---|---|
Demographics | pSS (n = 51) | nSS (n = 69) | p-Value | pSS (n = 17) | nSS (n = 15) | p-Value |
Age (years) | 51 ± 1.9 | 49 ± 1.4 | 0.24 a | 51.8 ± 3.2 | 42.1 ± 2.2 | 0.022 a |
Gender (% Fem) | 50/51 (98) | 64/69 (92.8) | 0.24 b | 16/17 (94) | 13/15 (87) | 0.58 b |
Race (%) | ||||||
White | 30/51 (59) | 35/69 (51) | 0.58 d | 11/17 (65) | 4/15 (24) | 0.09 d |
NatAm/> one c | 19/51 (37) | 29/69 (42) | 5/17 (29) | 10/15 (66) | ||
Black/Asian | 2/51 (4) | 5/69 (7) | 1/17 (6) | 1/15 (7) | ||
Ethnicity | ||||||
Hispanic | 2/51 (4) | 4/69 (6) | 1.0 b | 6/17 (35) | 7/15 (47) | 1.0 b |
Clinical Features | pSS | nSS | p-value b | pSS | nSS | p-value b |
FS+ (%) e | 32/51 (64) | 4/69 (6) | <0.0001 | 17/17 (100) | 0/15 (0) | <0.0001 |
Anti-Ro+ (%) f | 28/51 (55) | 4/69 (6) | <0.0001 | 13/17 (76) | 0/15 (0) | <0.0001 |
Anti-La+ (% +) f | 20/51 (39) | 1/69 (1) | <0.0001 | 4/17 (24) | 0/15 (0) | 0.104 |
WUSF+ (% +) g | 30/51 (59) | 32/69 (46) | 0.19 | 11/17 (65) | 3/15 (20) | 0.016 |
Schirmer’s+ (%) h | 19/51 (37) | 18/69 (26) | 0.23 | 6/17 (35) | 4/15 (27) | 0.712 |
vBS+ (%) i | 35/51 (69) | 26/69 (38) | 0.0009 | 12/17 (71) | 3/15 (20) | 0.006 |
Clinical Feature | Spearman’s Correlation a | Gamma Regression Model | ||
---|---|---|---|---|
r | p-Value | Model | Variable p-Value | |
vBS b | 0.43 | 7.2 × 10−7 | x + age | 6.7 × 10−5 |
x | 1.5 × 10−5 | |||
Schirmer’s test c | −0.087 | 0.34 | x + age | 0.73 |
x | 0.39 | |||
WUSF d | −0.09 | 0.31 | x + age | 0.77 |
x | 0.67 | |||
Biopsy Focus Score | 0.43 | 7.3 × 10−7 | x + age | 9.0 × 10−7 |
x | 2.3 × 10−8 | |||
Anti-Ro Ab e | 0.40 | 2.6 × 10−5 | x + age | 1.1 × 10−5 |
x | 3.0 × 10−6 | |||
Serum IgG | 0.38 | 1.7 × 10−5 | x + age f | 9.0 × 10−7 |
x | 1.4 × 10−5 |
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Joachims, M.L.; Leehan, K.M.; Dozmorov, M.G.; Georgescu, C.; Pan, Z.; Lawrence, C.; Marlin, M.C.; Macwana, S.; Rasmussen, A.; Radfar, L.; et al. Sjögren’s Syndrome Minor Salivary Gland CD4+ Memory T Cells Associate with Glandular Disease Features and Have a Germinal Center T Follicular Helper Transcriptional Profile. J. Clin. Med. 2020, 9, 2164. https://doi.org/10.3390/jcm9072164
Joachims ML, Leehan KM, Dozmorov MG, Georgescu C, Pan Z, Lawrence C, Marlin MC, Macwana S, Rasmussen A, Radfar L, et al. Sjögren’s Syndrome Minor Salivary Gland CD4+ Memory T Cells Associate with Glandular Disease Features and Have a Germinal Center T Follicular Helper Transcriptional Profile. Journal of Clinical Medicine. 2020; 9(7):2164. https://doi.org/10.3390/jcm9072164
Chicago/Turabian StyleJoachims, Michelle L., Kerry M. Leehan, Mikhail G. Dozmorov, Constantin Georgescu, Zijian Pan, Christina Lawrence, M. Caleb Marlin, Susan Macwana, Astrid Rasmussen, Lida Radfar, and et al. 2020. "Sjögren’s Syndrome Minor Salivary Gland CD4+ Memory T Cells Associate with Glandular Disease Features and Have a Germinal Center T Follicular Helper Transcriptional Profile" Journal of Clinical Medicine 9, no. 7: 2164. https://doi.org/10.3390/jcm9072164
APA StyleJoachims, M. L., Leehan, K. M., Dozmorov, M. G., Georgescu, C., Pan, Z., Lawrence, C., Marlin, M. C., Macwana, S., Rasmussen, A., Radfar, L., Lewis, D. M., Stone, D. U., Grundahl, K., Scofield, R. H., Lessard, C. J., Wren, J. D., Thompson, L. F., Guthridge, J. M., Sivils, K. L., ... Farris, A. D. (2020). Sjögren’s Syndrome Minor Salivary Gland CD4+ Memory T Cells Associate with Glandular Disease Features and Have a Germinal Center T Follicular Helper Transcriptional Profile. Journal of Clinical Medicine, 9(7), 2164. https://doi.org/10.3390/jcm9072164