B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren’s Disease: A Pilot Monocentric Exploratory Study
Abstract
:1. Introduction
2. Results
2.1. Baseline Demographic and Clinical Characteristics of Primary Sjögren’s Disease and Sicca Disease Cohorts
2.2. Primary Sjögren’s Disease and Sicca Disease Patients Showed Different Histological Features in Terms of Labial Salivary Glands’ CD20pos and CD138pos Cell Enrichment
2.3. miR-155 Is Overexpressed in the Labial Salivary Glands of Patients with Primary Sjögren’s Disease, Being Related to Lymphomagenesis and Degree of Focal Inflammation
2.4. BAFF-R and IL-6R Expression Are Upregulated in Labial Salivary Glands of Patients with Primary Sjögren’s Disease, Being Related to NHL Development and Directly Correlating with miR-155 Levels
3. Discussion
4. Materials and Methods
4.1. Patient Selection
4.2. Minor Salivary Glands Biopsy
4.3. Clinical and Immunological Assessment of Patient Cohorts
4.4. Immunohistochemistry of CD20 and CD138 in Labial Salivary Gland Tissue
4.5. miR-155, BAFF-R, and IL-6R Expression in Labial Salivary Gland Biopsy by qPCR
4.6. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variable | Sicca Disease (n = 20) | pSS Cohort (n = 24) | p | pSS without NHL Evolution (n = 19) | pSS with NHL Evolution (n = 5) | p * | p ** | p *** |
---|---|---|---|---|---|---|---|---|
Gender, female (%) | 19 (95.0) | 21 (87.5) | 0.39 | 17 (89.4) | 5 (100) | 0.45 | 0.52 | 0.62 |
Age (years) | 52.5 (40.3–57.3) | 54.5 (47.3–64.8) | 0.10 | 53.0 (46.0–61.0) | 67.0 (54.5–77.0) | 0.04 | 0.33 | 0.02 |
Disease duration (years) | - | 10.5 ± 3.4 | - | 12.3 ± 1.4 | 7.3 ± 3.1 | 0.13 | - | - |
Lymphocytic focus score (foci/4 mm2) | 0 | 3.5 ± 0.3 | <0.0001 | 3.6 ± 0.4 | 3.2 ± 0.6 | 0.64 | <0.0001 | <0.0001 |
ANA | 4 (20) | 24 (100) | <0.0001 | 19 (100) | 5 (100) | 1 | <0.0001 | <0.0001 |
Anti-Ro/SSA, n (%) | 0 (0) | 22 (92) | <0.0001 | 18 (95) | 4 (75) | 0.18 | <0.0001 | <0.0001 |
Anti-La/SSB, n (%) | 0 (0) | 20 (83) | <0.0001 | 17 (89) | 3 (60) | 0.13 | <0.0001 | 0.0003 |
RF-IgApos, n (%) | 0 (0) | 1 (0.04) | 0.93 | 1 (0.05) | 0 (0) | 0.96 | 0.92 | 1 |
RF-IgMpos, n (%) | 0 (0) | 3 (0.13) | 0.87 | 3 (0.16) | 0 (0) | 0.93 | 0.86 | 1 |
IgG (mg/dL) | 1147.7 ± 59.8 | 1247.7 ± 79.6 | 0.34 | 1184.6 ± 60.7 | 1468.8 ± 291.2 | 0.14 | 0.67 | 0.09 |
IgM (mg/dL) | 138.2 ± 12.6 | 119.5 ± 11.9 | 0.29 | 132.6 ± 12.8 | 69.4 ± 16.7 | 0.03 | 0.76 | 0.02 |
IgA (mg/dL) | 193.9 ± 20.4 | 228.8 ± 26.7 | 0.32 | 188.9 ± 20.1 | 380.6 ± 73.9 | 0.002 | 0.86 | 0.002 |
Gamma-globulin (%) | 14.3 ± 0.6 | 17.1 ± 0.9 | 0.02 | 15.9 ± 0.8 | 21.4 ± 1.8 | 0.006 | 0.12 | 0.0001 |
ALC (×109/L) | 2319.9 ± 304.3 | 1928.1 ± 77.4 | 0.18 | 1685.6 ± 90.8 | 1889.6 ± 126.7 | 0.29 | 0.06 | 0.49 |
C3 (mg/dL) | 109.3 ± 4.3 | 111.9 ± 3.8 | 0.65 | 112.4 ± 4.7 | 109.5 ± 4.1 | 0.76 | 0.63 | 0.98 |
C4 (mg/dL) | 21.7 ± 1.6 | 25.0 ± 2.2 | 0.25 | 22.6 ± 1.8 | 24.5 ± 6.7 | 0.70 | 0.71 | 0.54 |
CRP (mg/L) | 2.0 ± 0.6 | 1.9 ± 0.4 | 0.89 | 1.7 ± 0.3 | 3.1 ± 2.7 | 0.34 | 0.66 | 0.54 |
ESR (mm/1st h) | 14.1 ± 3.1 | 21.0 ± 2.8 | 0.11 | 19.3 ± 3.1 | 26.5 ± 6.8 | 0.31 | 0.24 | 0.09 |
ESSDAI | - | 2.8 ± 0.3 | - | 6.5 ± 2.7 | 8.7 ± 4.2 | 0.70 | - | - |
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Bruno, D.; Tolusso, B.; Lugli, G.; Di Mario, C.; Petricca, L.; Perniola, S.; Bui, L.; Benvenuto, R.; Ferraccioli, G.; Alivernini, S.; et al. B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren’s Disease: A Pilot Monocentric Exploratory Study. Int. J. Mol. Sci. 2024, 25, 3259. https://doi.org/10.3390/ijms25063259
Bruno D, Tolusso B, Lugli G, Di Mario C, Petricca L, Perniola S, Bui L, Benvenuto R, Ferraccioli G, Alivernini S, et al. B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren’s Disease: A Pilot Monocentric Exploratory Study. International Journal of Molecular Sciences. 2024; 25(6):3259. https://doi.org/10.3390/ijms25063259
Chicago/Turabian StyleBruno, Dario, Barbara Tolusso, Gianmarco Lugli, Clara Di Mario, Luca Petricca, Simone Perniola, Laura Bui, Roberta Benvenuto, Gianfranco Ferraccioli, Stefano Alivernini, and et al. 2024. "B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren’s Disease: A Pilot Monocentric Exploratory Study" International Journal of Molecular Sciences 25, no. 6: 3259. https://doi.org/10.3390/ijms25063259