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.

Primary Failure of Eruption (PFE) is a disorder characterized by aberrant tooth eruption, in which one or more teeth fail to follow the physiological eruptive pathway and remain partially or completely embedded within the bone or soft tissues. Although the etiopathogenesis of PFE is not yet fully elucidated, several contributing factors have been identified, including genetic alterations, hormonal disturbances, and systemic conditions. An expanding body of evidence points to the centrality of genetic determinants in the etiopathogenesis of PFE, supporting its occurrence in both syndromic contexts and non-syndromic presentations. Non-syndromic forms are closely related to heterozygous variants in the Parathyroid Hormone 1 Receptor (PTH1R) gene, located on chromosome 3p21, which encodes a receptor essential for the regulation of bone and dental growth and development. In most cases, pathogenic variants result in a non-functional receptor. To date, a substantial number 50 PTH1R variants have been documented in individuals exhibiting a phenotype consistent with PFE, underscoring the central involvement of this gene in the disorder’s molecular basis. Advances in understanding the genetic contribution to PFE emphasize the need for early diagnosis, as timely identification of the condition can prevent secondary dental complications and reduce reliance in adulthood on invasive orthodontic or surgical interventions, including extractions, orthognathic surgery, and implant-supported rehabilitation. This review aims to provide a comprehensive analysis of the spectrum of PTH1R variants implicated in PFE, examining genotype–phenotype correlations and their implications for diagnostic strategies and clinical management.

Fragile X syndrome (FXS) and related conditions associated with FMR1 gene alterations have increasingly been linked to mitochondrial dysfunction, although most available evidence derives from peripheral cell models. Whether these abnormalities also occur in disease-relevant neuronal populations remains largely unknown. Building on our previous observations in patient-derived fibroblasts, we investigated mitochondrial structure and function in neurons differentiated from induced pluripotent stem cells (iPSCs) generated from individuals with FXS and carriers of unmethylated full mutations, using matched healthy control lines. Mitochondrial integrity, bioenergetic properties, and network organization were evaluated to determine whether FMR1-associated mitochondrial defects are preserved in a neuronal context. Mitochondrial abnormalities previously identified in fibroblasts were recapitulated in iPSC-derived neurons. These findings demonstrate that impaired mitochondrial dynamics and function are conserved across different cell types, indicating that mitochondrial dysfunction represents a relevant cellular feature of FXS and related FMR1-associated conditions. Our results indicate that mitochondrial dysfunction is a shared feature of FMR1-related neuronal models, while the underlying patterns of mitochondrial remodeling are influenced by the specific FMR1-associated condition. These results support a role for mitochondrial alterations in FMR1-related neuronal dysfunction and provide a basis for the further investigation of the mechanisms linking mitochondrial homeostasis to the pathophysiology of FXS and related conditions.