Increasing evidence underlines the role of B-cells in the development of hepatic fibrogenesis following viral infections and metabolic dysfunction, through different mechanisms depending on the etiology. Circulating biomarkers of B-cell activation—such as B-cell activating factor (BAFF), immunoglobulin G (IgG) subclasses, and free light chains (FLCs)—may be associated with different results between viral and metabolic hepatic fibrosis, supporting their use as diagnostic tools. We conducted a case-control study including 100 patients with liver fibrosis, 50/100 of metabolic etiology and 50/100 of viral etiology. A reference group of 30 healthy donors was included as control. Serum levels of BAFF were measured using ELISA, while IgG subclasses (IgG1, IgG2, IgG3, IgG4), κ-FLC, λ-FLC, and the κ/λ ratio were quantified by turbidimetric methods. In univariate analysis, κ-FLC, λ-FLC, and BAFF levels were significantly elevated in both patient groups, with the highest concentrations consistently observed in metabolic fibrosis. IgG2 was selectively increased in metabolic fibrosis, whereas IgG3 was specifically elevated in viral fibrosis. Multivariate analysis confirmed these findings, showing a clear clustering of the three groups and identifying increased BAFF and κ-FLC as key features of metabolic fibrosis, while elevated IgG3 emerged as the most distinctive marker of viral etiology. These results reveal distinct B-cell-related immunological signatures in metabolic and viral hepatic fibrosis supporting the role of BAFF, FLCs, and IgG subclasses as biomarkers of etiological differentiation, and provide novel insights into the immune mechanisms driving fibrosis progression, potentially contributing to the identification of new therapeutic targets.

A monocentric cross-sectional study was performed to investigate the role of serum calprotectin as a biomarker for disease severity and activity in systemic sclerosis (SSc). Serum calprotectin was measured in 74 consecutive SSc patients admitted to a tertiary hospital in Rome, and in 50 healthy controls (HCs) who were healthcare workers, using Aptiva’s particle-based multianalyte technology. In SSc patients, a statistically significant correlation was found between calprotectin and the modified Rodnan skin score (mRSS) (r = 0.402, p < 0.001), disease activity index (DAI) (r = 0.420, p < 0.001), disease severity scale (DSS) (r = 0.365, p < 0.01), forced vital capacity (FVC) (r = −0.459, p < 0.001), and diffusion lung capacity for carbon monoxide (DLco) (r = −0.445, p < 0.001). Calprotectin was higher in SSc patients with digital ulcers (DUs) than in SSc patients without DUs [2.98 mcg/mL (IQR 2.07;4.29) vs. 2.08 mcg/mL (IQR 1.71;2.45), p < 0.01] and in SSc patients with interstitial lung disease (ILD) compared to SSc patients without ILD [2.56 mcg/mL (IQR 1.94;3.03) vs. 1.96 mcg/mL (IQR 1.7;2.35), p < 0.01]. The multivariable stepwise logistic regression analysis showed calprotectin to be independently associated with DUs [OR 2.531 (CI 95%: 1.074;5.961), p < 0.05] and ILD [OR 3.687 (CI 95%: 1.336;10.170), p < 0.05] in SSc patients. Serum calprotectin is associated with DUs and ILD in SSc patients.

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.