Lack of Syndecan-1 promotes the pathogenesis of experimental rheumatoid arthritis

Jurjus, Rosalyn; Dosh, Laura; Farhat, Rima; Daccache, Tatiana; El Masri, Jad; Ghazi, Maya; Hawi, Jihad; Leone, Angelo; Jurjus, Abdo

doi:10.1007/s00251-024-01337-9

Cited by 2 publications

(6 citation statements)

References 22 publications

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“…Specifically, research by Salminen-Mankonen et al [35] demonstrated an increase in SDC-1 expression in chondrocytes from cartilage that was damaged in the early stages of osteoarthritis, suggesting a potential involvement in the mechanisms that repair damaged joints. Jurjus et al found that the absence of SDC-1 in a collagen IIinduced arthritis mouse model led to more severe symptoms of rheumatoid arthritis, characterized by increased bone erosion, cartilage destruction, inflammation, and elevated TNF-α levels, confirming the SDC-1 protective role in this pathological setting [15]. Consistently, it has been shown that antirheumatic drugs decrease the serum level of SDC-1, which might reflect a decrease in shedding [26].…”

Section: Discussionmentioning

confidence: 87%

“…SDC-1, a member of the transmembrane proteoglycans, plays a significant role in the context of autoimmune diseases, with its complex involvement in both inflammation and tissue repair [15,20,22,25,[30][31][32]. Its ability to interact with a wide range of ligands is closely associated with its ectodomain, which encompasses chondroitin and heparan sulphate chains (Figure 1) [20].…”

Section: Discussionmentioning

confidence: 99%

“…Sera from 50 sex-and age-matched healthy blood donors (HD) were tested as control. Inclusion criteria of RA patients: positivity for antibodies against cyclic citrullinated peptide (anti-CCP) at high levels, for Rheumatoid Factor (RF) and antinuclear antibodies (ANA) detected by indirect immunofluorescence assay (IIFA) on HEp-2 cells with a titer of 1:320 and with pattern coarse speckled [15].…”

Section: Patientsmentioning

confidence: 99%

“…Inclusion criteria of SLE patients: ANA positive at titres ≥1:640 with homogeneous pattern, positive with an immunofluorescence assay for antibodies to native DNA, using the kinetoplast of Crithidia luciliaea substrate [15].…”

Section: Patientsmentioning

confidence: 99%

“…Emerging research has begun to highlight other biomarkers with significant implications for autoimmunity, including Syndecan-1 (SDC-1) [13][14][15]. Also known as CD138, SDC-1 is a transmembrane heparan sulfate proteoglycan ubiquitously found on the cell surface and nuclear membrane (Figure 1) [16].…”

Section: Introductionmentioning

confidence: 99%

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Spotlight on Syndecan 1 Role in Systemic Autoimmune Rheumatic Diseases: Main Actor or Guest Appearance?

Carnazzo,

Gulli,

Basile

et al. 2024

Preprint

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Background: Systemic autoimmune rheumatic diseases (SARDs), including Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA), are characterized by chronic inflammation and autoimmunity. Identifying reliable biomarkers is crucial for enhancing diagnosis, monitoring disease progression, and evaluating therapeutic responses. This study explores the potential of serum Syndecan-1 (SDC-1) as a biomarker for these conditions and concurrently examines its relationship with free light chain (FLC) expression levels in the same patients. Methods: A retrospective analysis was performed on serum samples from 120 patients (60 RA, 60 SLE), alongside 50 healthy donors (HD). Serum levels of κ and λ FLCs were determined by turbidimetric assay, while SDC-1 levels were measured using ELISA. Statistical analyses, including the Kruskal-Wallis test, Wilcoxon-Mann-Whitney U test, multivariable linear regression and Spearman’s correlation, were employed to compare biomarker levels across groups and to explore correlations among them. Results: Significantly increased levels of SDC-1, κ-FLC, and λ-FLC were observed in patients diagnosed with RA and SLE compared to HD (p < 0.001), while no significant differences in the κ/λ ratio were noted among the groups (p = 0.4). A statistically significant difference in subject age was also identified. However, multivariate regression analysis indicated that RA and SLE statuses are significantly associated with the levels of these markers, with minimal confounding by age. A significant correlation was observed separately in all groups between the FLC markers. Conversely, no correlation was detected between SDC-1 and FLCs, nor between these markers and age. Conclusion: Elevated serum levels of FLCs and SDC-1 in RA and SLE patients compared to healthy controls underscore their potential as biomarkers for SARDs. The findings also suggest sustained plasma cells activation, supporting the SDC-1 role in the pathogenesis of these conditions.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Spotlight on Syndecan 1 Role in Systemic Autoimmune Rheumatic Diseases: Main Actor or Guest Appearance?

Carnazzo,

Gulli,

Basile

et al. 2024

Preprint

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Syndecan-1 Levels in Females with Active Rheumatoid Arthritis

Rodriguez-Jimenez,

Gonzalez-Ponce,

Gamez-Nava

et al. 2024

JCM

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Background: The relationship between serum glycoprotein syndecan-1 and disease activity in rheumatoid arthritis (RA) is still unknown. This study aimed to evaluate whether serum syndecan-1 concentrations are associated with moderate/severe disease activity. Methods: Study Design: This was a cross-sectional study. Seventy-five adult women with RA were classified into (a) moderate/severe RA based on the disease activity score, using the erythrocyte sedimentation rate (DAS28-ESR ≥ 3.2, n = 50), and (b) RA in remission (DAS28-ESR < 2.6, n = 25). Twenty-five healthy women were taken as the reference group. Syndecan-1 levels were determined using enzyme-linked immunosorbent assay (ELISA). High values of serum syndecan-1 levels (≥24 ng/mL) were used to identify the utility values of this biomarker. Results: The patients with RA had higher levels of syndecan-1 than the controls (p < 0.001). RA patients with active disease had higher syndecan-1 levels than RA patients in remission (57.6 vs. 23.5 ng/mL, respectively; p = 0.002). High syndecan-1 concentrations demonstrated the following utility values for identifying disease activity: sensitivity, 84% (95%CI: 71–93); specificity, 52% (95%CI: 31–72); positive predictive value, 78% (95%CI: 70–84); and negative predictive value, 62% (95%CI: 44–77). Conclusions: High syndecan-1 levels have good sensitivity and positive predictive value for identifying disease activity; however, their specificity is limited. Future prospective studies are needed to assess whether syndecan-1 levels can predict treatment failure in RA.

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Lack of Syndecan-1 promotes the pathogenesis of experimental rheumatoid arthritis

Cited by 2 publications

References 22 publications

Spotlight on Syndecan 1 Role in Systemic Autoimmune Rheumatic Diseases: Main Actor or Guest Appearance?

Spotlight on Syndecan 1 Role in Systemic Autoimmune Rheumatic Diseases: Main Actor or Guest Appearance?

Syndecan-1 Levels in Females with Active Rheumatoid Arthritis

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