Insights into Patient Heterogeneity in Sjögren’s Disease
Abstract
1. Introduction
2. The Need for Patient Stratification in Sjögren’s Disease
3. Interferon Signatures in Patients with SjD
4. Symptom-Based Stratification Approaches
4.1. The Newcastle Sjogren’s Stratification Tool
4.2. Therapeutic Significance of Patient Stratification Based on Patient-Reported Symptoms
4.3. Patient Stratification Based on the Patient-Reported Symptoms Dryness, Fatigue, and Pain
4.4. Cluster Analysis Based on Patient-Reported Symptoms and Clinical and Biological Manifestations
4.5. Patient Group Classification in Clinical Routine Practice
5. Molecular Stratification Approaches
5.1. Advantages of Molecular Stratification Approaches
5.2. Transcriptome Analysis of Peripheral Blood Samples
5.3. Multi-Omics Profiling of Whole Blood Samples
6. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Reference | Characteristics | Cluster 1 | Cluster 2 | Cluster 3 | Cluster 4 | Cluster 5 |
---|---|---|---|---|---|---|
Nguyen et al. [12] | BALS B-cell-active disease with low symptom levels | HAS High systemic disease activity | LSAHS Low systemic activity; high symptom burden | - | - | |
Clinical features | Low ESSPRI, low ESSDAI, high frequency of lymphomas | High symptom burden of dryness, fatigue, and lower-body pain; high systemic disease activity | Hish ESSPRI, low ESSDAI, no lymphomas | - | - | |
Laboratory features | High frequency of anti-SSA/Ro and anti-SSB/La antibodies and RF | Anti-RNP and anti-centromere antibodies | Lower frequency of anti-SSA/Ro and anti-SSB/La antibodies | - | - | |
Transcriptomic features | IL-7, TNF-RII, CXCL13, and high IFN signatures | IL-7, TNF-RII, and CXCL13 | Low IFN signatures | - | ||
Tarn et al. [13] | LSB Low symptom burden | HSB High symptom burden | DDF Dryness dominant with fatigue | PDF Pain dominant with fatigue | - | |
Clinical features | Highest prevalence of lymphoma | - | - | |||
Laboratory features | Higher rates of anti-SSA/Ro and anti-SSB/La positivity | Higher rates of anti-SSA/Ro and anti-SSB/La positivity | - | - | ||
Transcriptomic features | CXCL13, b2-microglobulin | |||||
Fang et al. [14] | C1 “low systemic activity” | C2 “inflammatory” | C3 “high systemic activity, inflammation” | C4 “high systemic activity, non-inflammation” | Moderate burden, multi-organ involvement | |
Clinical features | Minimal systemic involvement, lowest ESSDAI scores | Serological changes, joint involvement, no systemic manifestations | High symptom burden, highest rate of fatigue | Joint and hematological involvement, highest ESSDAI scores, highest rates of dryness and fatigue | Articular and glandular involvement, high physical fatigue, highest pain | |
Laboratory features | Lowest titers of autoantibodies | Highest positivity rates for ANA, SSA/Ro, and SSB/La antibodies | Highest rates of RF positivity | - | ||
Transcriptomic features | Decreased expression of modules associated with inflammation, monocytes, and T cells | Increased IFN signaling, elevated levels of cytokines and chemokines, overexpression of modules related to B and T cells, cellular growth, and metabolism | Increased IFN signaling, increased expression of modules associated with inflammation, monocytes, and T cells, downregulation of genes associated with neutrophil activation | Downregulation of most modules associated with inflammation, monocytes, and lymphocytes, overexpression of modules related to prostaglandins and cellular respiration | - | |
James et al. [15] | C1 | C2 | C3 | - | ||
Clinical features | Highest fatigue and joint pain, low dryness | Highest dryness, slightly higher ESSDAI scores | Low fatigue and joint pain | - | ||
Laboratory features | Higher rates of anti-SSB/La positivity | - | ||||
Transcriptomic features | Low IFN signature, low inflammation | Highest levels of BAFF, CXCL10, and CXCL9, high levels of CXCL13 | High levels of CXCL13 and CXCL10, highest levels of TNF-RII and sE-selectin, low inflammation | - | ||
Barturen et al. [16] | Inflammatory | Lymphoid | Interferon | Undefined | ||
Clinical features | Fibrosis complications | Less aggressive phenotypes | Most severe phenotypes | Some clinical complications | ||
Laboratory features | Elevated ACPA, anti-centromere B, and IgM anti-phosphorylcholine natural antibodies | Slightly enriched in ACPA, anti-centromere, and IgM anti-phosphorylcholine natural antibodies | Elevated levels of anti-dsDNA, anti-SSA/Ro, anti-SSB/La, and anti-U1-RNP antibodies | |||
Transcriptomic features | Increased MMP-8, IL-1RA, and CXCL13 | Increased CXCL10, BAFF, MCP2, TNF, IL1-RA, and CXCL13, association with HLA-class II genes | Nonspecific molecular patterns | |||
Soret et al. [17] | C1 “interferon” | C2 “healthy like”) | C3 “intermediate IFN” | C4 “low IFN, inflammatory” | ||
Clinical features | Lowest ESSDAI scores, patients with glandular manifestations | Highest ESSDAI scores, patients with glandular manifestations | ||||
Laboratory features | Higher levels of ENA, anti-SSA/Ro, and anti-dsDNA antibodies, κ-FLC, and RF | Higher levels of ENA, anti-SSA/Ro, and anti-dsDNA antibodies and c κ-FLC | ACPA | |||
Transcriptomic features | Highest IFN signature (type I + II), increased CXCL10, MCP2, TNFa, CXCL13, IL-6, IL-1RA, and BAFF | Weak type I + II IFN signatures, increased CXCL10, CXCL13, and BAFF compared to healthy controls | “Intermediate” high IFN signature (type I > type II), upregulation of IL-7-signaling, LXRL/RXR activation, higher levels of CXCL10, MCP2, TNFa, CXCL13, and BAFF | “Low” increase in IFN signatures (type II > type I), increased levels of CXCL10, CXCL13, and BAFF, downregulation of TGFb-associated modules |
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Pecorelli, L.; Klein, K. Insights into Patient Heterogeneity in Sjögren’s Disease. Int. J. Mol. Sci. 2025, 26, 6367. https://doi.org/10.3390/ijms26136367
Pecorelli L, Klein K. Insights into Patient Heterogeneity in Sjögren’s Disease. International Journal of Molecular Sciences. 2025; 26(13):6367. https://doi.org/10.3390/ijms26136367
Chicago/Turabian StylePecorelli, Lisa, and Kerstin Klein. 2025. "Insights into Patient Heterogeneity in Sjögren’s Disease" International Journal of Molecular Sciences 26, no. 13: 6367. https://doi.org/10.3390/ijms26136367
APA StylePecorelli, L., & Klein, K. (2025). Insights into Patient Heterogeneity in Sjögren’s Disease. International Journal of Molecular Sciences, 26(13), 6367. https://doi.org/10.3390/ijms26136367