Objectives: Cryoglobulinemia (CG) is marked by abnormal immunoglobulins (Ig) in serum, precipitating at temperatures below 37 °C. Current classification categorizes CG into three subtypes (types I, II, and III) based on Ig clonality. The features distinguishing patients with CG based on their etiology remain unidentified. Aiming to characterize clinical and serological profiles of CG individuals, we conducted an observational analysis of a large cohort of patients and compared their characteristics based on underlying causes: hepatovirus (HV) infections, rheumatic diseases (RD), hematological disorders, and unidentified etiology (essential CG). Methods: We analyzed 252 cryoglobulin-positive serum samples from 182 patients and classified these into the four etiological groups. A separate sub-analysis was carried out for 10 patients meeting criteria for multiple diseases. We collected demographic, clinical, and laboratory data: CG characterization, complement (C3 and C4) levels, antinuclear antibodies (ANA), and rheumatoid factor (RF). Kruskal–Wallis and Wilcoxon–Mann–Whitney U-tests were used for comparisons. Results: Most patients (93.3%) had mixed cryoglobulinemia (types II + III), with 6.7% having type I. HV infection, predominantly hepatitis C, was the main (52.9%) associated condition within the cohort, followed by rheumatic (27.3%) and hematological (9.8%) disorders. In our cohort, ANA were frequent (45.3%) and often associated with RF positivity (43.6%) and decreased complement levels (C3: 42.4%, C4: 32.5%). Essential CG and CG associated with RD had a higher prevalence of cutaneous manifestations (p < 0.01) and renal involvement (p = 0.017). Hematological disorder-related CG showed higher cryoglobulin and RF concentrations (p < 0.01), despite milder symptoms. Conclusions: Our study underscores a mixed prevalence of CG across disease subgroups, with hepatitis-C virus as the primary factor, followed by rheumatic and hematological disorders. Four clinical and serological profiles of CG were identified based on their etiologies.

Introduction: We conducted a comprehensive comparative analysis of the Okazaki, Umehara, and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for diagnosing immunoglobulin G4-related disease (IgG4-RD). Materials and Methods: A retrospective study was conducted in a single tertiary hospital, using expert clinical judgment as the gold standard. We compared the diagnostic accuracy of the Okazaki, Umehara, and ACR/EULAR criteria in a cohort of 41 patients with suspected IgG4-RD. We assessed sensitivity, specificity, and positive and negative predictive values for each criterion, and conducted a separate analysis based on four IgG4-RD subtypes. Results: A total of 30 patients were confirmed to have IgG4-RD and 11 were identified as mimickers. The Umehara criteria demonstrated the highest sensitivity (83.33%), followed by the ACR/EULAR 2019 (66.67%) and Okazaki (60.0%) criteria. All three criteria exhibited 100% specificity, with overall diagnostic accuracy ranging from 70% to 88%. The areas under the curve (AUC) were 0.917 (Umehara), 0.800 (Okazaki), and 0.833 (ACR/EULAR 2019), indicating significant diagnostic effectiveness (p < 0.000). Subtype analysis revealed that the Umehara and ACR/EULAR 2019 criteria were more effective in diagnosing pancreato-hepato-biliary involvement (subtype 1), while the Okazaki and ACR/EULAR 2019 criteria were more effective in diagnosing retroperitoneal fibrosis and/or aortitis (subtype 2). Conclusions: Our study provides valuable insights into the diagnostic performance of the Okazaki, Umehara, and ACR/EULAR criteria for a cohort of patients with suspected IgG4-RD. The Umehara criterion demonstrated the highest sensitivity, suggesting its potential utility for screening purposes, while all three criteria showed consistent specificity.

Background and Objectives: IgG4-related disease is a chronic fibro-inflammatory condition. Despite the development of classification and responder indexes, reliable biomarkers for disease activity and therapeutic monitoring remain limited. We evaluate the performance of a panel of biomarkers, including cytokine profiles, plasmablasts and conventional markers. Materials and Methods: We conducted a cross-sectional, single-center study, involving 35 patients diagnosed with IgG4-RD. Disease activity was evaluated using the IgG4-RD Responder Index (RI), Damage Index (DI) and clinical assessment. Laboratory evaluation included serum IgG4, total IgG, CRP, ESR, eosinophils, IgE, complement levels, and cytokine profiling via multiplex immunoassay. B cell subpopulations were analyzed by flow cytometry. Statistical analyses were performed using STATA/BE 17.0. Results: Patients with active disease (RI > 4 or clinical judgment) exhibited significantly higher levels of total IgG (p = 0.02), IgG4 (p = 0.01), and IL-5 (p = 0.03). PET-positive patients showed a Th1-skewed immune profile, with elevated IFN-γ/IL-4 (p < 0.001), reduced IL-21/IFN-γ (p = 0.03), and increased eosinophils (p = 0.03). Clinician-assessed active disease was associated with higher total IgG levels (p = 0.01). Treatment-specific effects were observed: prednisone was associated with lower IgG4 and C3 levels. Notably, plasmablasts did not consistently correlate with clinical or imaging activity scores, possibly reflecting treatment status or B cell dynamics. Conclusions: This study demonstrates that cytokine ratios, particularly those involving IL-5, IL-13, IL-21, and IFN-γ, offer complementary information to traditional serological markers for IgG4-RD activity. While PET/CT-defined activity was best reflected by biomarkers of an IFN-γ-mediated pathway, the IgG4-RD RI demonstrated a stronger association with conventional humoral markers like serum IgG4 and total IgG. None of these biomarkers correlated with organ damage.

Background: Early identification of risk factors for low bone mass for chronological age (LBMca) and childhood osteoporosis (cOP) in patients undergoing skeletal growth is essential to mitigate long-term skeletal complications. cOP is diagnosed when LBMca (BMD Z-score ≤2) is accompanied by a clinically significant fracture history, or when vertebral fragility fractures are present.Methods: Patients under 21 years of age with at least one risk factor for LBMca (malabsorption syndrome, chronic inflammatory diseases, hematological diseases, endocrinopathies, drugs that affect bone metabolism, or insufficient calcium intake) were included. Data on fractures history and physical activity levels were collected. Spine and whole-body dual-energy x-ray absorptiometry (DXA) and vertebral morphometry were performed. Age-adjusted linear regression analysis evaluated associations between bone mineral density (BMD) and risk factors.Results: A total of 103 patients were included (mean age 9.8 years; 52.4% female), and 96.1% had more than two risk factors. The prevalence of LBMca was 10.5% and the prevalence of cOP was 4.8%. Vertebral BMD was positively associated with male sex. Whole body BMD was negatively associated with sedentary lifestyle and fracture history. Total body less head BMD showed negative associations with current steroid treatment, sedentary lifestyle, and history of fractures.Conclusions: Pediatric populations at risk of LBMca or cOP often have multiple risk factors, notably modifying ones such as physical inactivity. Up to 10.5% of children with risk factors present LBMca and 4.8% have an undiagnosed or unknown cOP. Longitudinal studies are warranted to understand the long-term impact of the identified risk factors, including age, sex, sedentary lifestyle, ethnicity and vitamin D status, on bone health.

Objectives: To evaluate the relationship between IFN-related gene (IRG) expression and disease activity, organ involvement and serological subgroups in JDM and to assess its potential as a biomarker for disease monitoring and treatment response. Methods: Patients with JDM enrolled in a single-centre cohort were assessed using standardized clinical measures, including physician’s global assessment (PGA), Childhood Myositis Assessment Scale (CMAS), Manual Muscle Testing (MMT8) and modified skin disease activity score. Associations between IRG expression and clinical features were analysed using correlation analyses and mixed-effects models. Longitudinal trajectories of disease activity were explored using latent class mixed models. Results: Seventy-four patients contributed 158 samples. Expression of type-I IRGs (IFI27, IFI44L, IFIT1, RSAD2, SIGLEC1) and CXCL10 was significantly higher in active disease and correlated with muscle and skin disease activity. IRG expression inversely correlated with CMAS and MMT8 and positively with mDAS. Distinct organ-specific associations were identified: CXCL9 expression was associated with interstitial lung disease, while IL-18 was associated with calcinosis, cutaneous ulceration and gastrointestinal involvement. Higher IRG expression was observed in patients with anti-MDA5 and anti-NXP2 autoantibodies. Longitudinal analyses demonstrated that IRG expression paralleled disease activity trajectories and decreased in patients achieving inactive disease, including those treated with baricitinib. Conclusion: IFN pathway activation is closely associated with disease activity and organ involvement in JDM. IRG expression reflects dynamic changes in disease status and may serve as a clinically useful biomarker for monitoring disease activity, stratifying patients by organ involvement and supporting response assessment to targeted therapies.