Autoimmune diseases represent a severe personal and healthcare problem that seeks novel therapeutic solutions. Mesenchymal stem cells (MSCs) are multipotent cells with interesting cell biology and promising therapeutic potential. The immunoregulatory effects of secretory factors produced by umbilical cord mesenchymal stem cells (UC-MSCs) were assessed on B lymphocytes from 17 patients with systemic lupus erythematosus (SLE), as defined by the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE, and 10 healthy volunteers (HVs). Peripheral blood mononuclear cells (PBMCs) from patients and HVs were cultured in a UC-MSC-conditioned medium (UC-MSCcm) and a control medium. Flow cytometry was used to detect the surface expression of CD80, CD86, BR3, CD40, PD-1, and HLA-DR on CD19+ B cells and assess the percentage of B cells in early and late apoptosis. An enzyme-linked immunosorbent assay (ELISA) quantified the production of BAFF, IDO, and PGE2 in PBMCs and UC-MSCs. Under UC-MSCcm influence, the percentage and mean fluorescence intensity (MFI) of CD19+BR3+ cells were reduced in both SLE patients and HVs. Regarding the effects of the MSC secretome on B cells in lupus patients, we observed a decrease in CD40 MFI and a reduced percentage of CD19+PD-1+ and CD19+HLA-DR+ cells. In contrast, in the B cells of healthy participants, we found an increased percentage of CD19+CD80+ cells and decreased CD80 MFI, along with a decrease in CD40 MFI and the percentage of CD19+PD-1+ cells. The UC-MSCcm had a minimal effect on B-cell apoptosis. The incubation of patients’ PBMCs with the UC-MSCcm increased PGE2 levels compared to the control medium. This study provides new insights into the impact of the MSC secretome on the key molecules involved in B-cell activation and antigen presentation and survival, potentially guiding the development of future SLE treatments.

Granulomatosis with polyangiitis (GPA) is a representative of vasculitides associated with anti-neutrophil cytoplasmic autoantibodies. “Classical” antibodies directed against proteinase 3 are involved in the pathogenesis and are part of the GPA diagnosis at the same time. Along with them, however, antibodies against Lysosomal-Associated Membrane Protein-2 (LAMP-2) and antibodies directed against plasminogen have been described in GPA. Objectives and methodology: We performed a cross-sectional study enrolling 34 patients diagnosed with GPA. Our study was aimed at looking for correlations between serum levels of LAMP-2 and plasminogen and the clinical manifestations of the GPA. Furthermore, we examined serum levels of tumor necrosis factor-alpha (TNF-α) and its associated indoleamine-pyrrole 2,3-dioxygenase (IDO), as well as we looked for a correlation between these cytokines and the clinical manifestations of GPA. The results showed that in GPA, serum plasminogen levels were negatively associated with renal involvement (receiver operating characteristic (ROC) area under the curve (AUC) of 0.78) (95% CI 0.53–0.91), p = 0.035, and the extent of proteinuria, Spearman’s Rho = –0.4, p = 0.015. Increased levels of TNF-α and IDO correlated with disease activity, Spearman’s Rho =0.62, p = 0.001 and Spearman’s Rho = 0.4, p = 0.022, respectively, whereas only TNF-α was increased in severe forms of GPA with lung involvement (ROC AUC of 0.8) (95% CI 0.66–0.94), p = 0.005. In this study, we demonstrate the alteration of soluble factors, which play an important role in the pathogenesis of GPA and their relationship with the clinical manifestations of the disease. Our main results confirm the associations of increased secretory TNF-α and some clinical manifestations, and we describe for the first time decreased serum plasminogen levels and their association with renal involvement.

Background: Screening for presymptomatic type 1 diabetes (T1D) reduces the risk of diabetic ketoacidosis (DKA) and allows for early intervention with disease-modifying therapies. Despite the rising incidence of T1D in Bulgaria, screening initiatives remain limited. This pilot study aims to evaluate the feasibility of selective T1D screening in high-risk children and identify potential clinical associations with islet autoimmunity. Methods: The study targeted a recruitment of 250 children aged 0–18 years (200 with a relative with T1D and 50 without). Screening for islet autoantibodies (AABs), including glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated-2 (IA-2A), zinc transporter-8 (ZnT8A), and islet cell cytoplasmic autoantibodies (ICAs), was performed via chemiluminescence immunoassay (CLIA). Participants testing positive for one or more AABs were scheduled for longitudinal immunological and metabolic follow-up to evaluate the persistence of autoimmunity and disease progression. Results: Between October 2024 and February 2026, the pilot study recruited 210 participants (84% of the 250 target), including 160 children with a relative (target 200) and 50 without a family history of T1D (target 50). Within the high-risk group, seven children (4.4%) tested positive for a single autoantibody (3 GADA, 2 ZnT8A, 1 IA-2A, and 1 IAA), while no autoantibodies were detected in the group without a relative. No cases of multiple autoantibody positivity or stage 3 T1D were identified in either group. Furthermore, no statistically significant associations were observed between autoantibody positivity and secondary factors, including breastfeeding, allergic status, a high-glycemic diet, frequent illness, and personal history of autoimmune disease. Conclusions: The findings validate the feasibility of selective T1D screening in Bulgaria, driven by high public interest and successful recruitment across both high-risk and general population cohorts. While this exploratory study found no significant clinical correlations, it establishes a vital roadmap for larger, longitudinal research. Ultimately, this pilot framework provides a scalable model for implementing standardized early detection to reduce the burden of T1D on the national healthcare system.

The aim of this study was to obtain and characterize grape seed extract and to demonstrate its potential immunomodulatory properties in the autoimmune disease systemic lupus erythematosus (SLE). A Syrah grape seed extract was obtained using 70% aqueous ethanol, magnetic stirrer, 3 h. The obtained extracts were concentrated by vacuum evaporation and dryer at 40 °C. The total phenolic content (TPC), the total amount of flavonoids (TF) and procyanidins (PC), and the antioxidant (AO) capacity of the extract were determined by spectrophotometric methods. The individual composition of the extract was demonstrated by the high-performance liquid chromatography (HPLC) method. The effect of grape seed extract (GSE) on peripheral blood mononuclear cells (PBMC) from healthy donors and patients with SLE was studied to compare Th1 and Th2 subsets and their expression of key activation markers—CD25 and HLA-DR. PBMC were cultured in the presence or absence of GSE, and the effects on Th1 and Th2 cells were analyzed by flow cytometry. GSE treatment increased the proportion of Th1 cells in both healthy individuals and SLE patients. In addition, a significant upregulation of the late activation marker HLA-DR was observed on Th1 cells obtained from patients with systemic lupus erythematosus (SLE). No significant effects were found on Th2 cell populations. These findings indicate that GSE can stimulate Th1-mediated immune responses in SLE, proving its potential immunomodulatory properties beyond its known antioxidant effects.

Усложнените клинични случаи на пациенти с автореактивна имунна система, способна да нанесе вреда на организма, налагат задълбочено изследване на основните имунопатогенетични механизми, последвано от намиране на пътища за разработването на ефективни терапевтични стратегии. В момента най-често използваните терапевтични алтернативи имат тежки странични ефекти и намалена ефективност след продължително лечение на пациенти с автоимунни заболявания. Секретомът на мезенхимните стволови клетки (МСК-секретом) съдържа съединения с потенциални терапевтични приложения, една обещаваща нова клинична стратегия за лечение. Данните, представени в този литературен преглед, обобщават информация от експериментални изследвания и малкото натрупани знания от клиничната практика, както и повдигат въпроси относно ролята на съвременните, иновативни терапии за подпомагане на автоимунни пациенти. A thorough investigation of the underlying immunopathogenetic pathways is required in order to create effective therapeutic methods for the complex clinical cases of patients with an autoreactive immune system that can harm the organism. Currently, the most commonly used therapeutic alternatives have severe side effects and reduced effectiveness after long-term treatment of patients with autoimmune diseases. The secretome of mesenchymal stem cells (MSCs-secretome) does, however, contain compounds with potential therapeutic applications, a promising new clinical strategy for treating the aforementioned patients. The data presented in this review summarizes information from experimental research and a small amount of clinical practice knowledge. It also raises fundamental questions regarding the role of modern, innovative therapies in helping autoimmune patients.

Background: Type 1 diabetes (T1D) incidence is rising at 3–5% per year. Autoantibody (AAB) screening identifies at-risk children pre-symptomatically, yet the clinical significance of single AAB positivity and its short-term trajectory remain incompletely characterized. Methods: Five T1D-associated AABs (anti-GAD65, anti-IA2, anti-ZnT8, ICA, IAA) were measured in 210 Bulgarian children (160 with first-degree T1D relatives, 50 controls). Seven single-AAB-positive children received lifestyle counseling (low-glycemic-index diet, physical activity ≥ 60 min/day) and were reassessed at 3 or 6 months with repeat AAB panels, HbA_1c, blood glucose and C-peptide. Results: Anti-GAD65 was the most frequent single AAB (n = 3), followed by anti-ZnT8 (n = 2), anti-IA2 (n = 1) and IAA (n = 1). None developed a second AAB or metabolic abnormalities. Titer dynamics were heterogeneous: two children showed apparent seroreversion (in one, substantially confounded by concurrent immunosuppressive therapy for an unrelated condition), one showed a ~15-fold titer reduction while remaining seropositive, one showed a minimal titer decrease, and three displayed mildly increasing titers. None progressed to multiple autoantibody positivity, and all maintained normal metabolic profiles. Conclusions: Favorable short-term outcomes were observed during follow-up of children with single autoantibody positivity. These findings suggest that single AAB positivity may follow a non-progressive course in some children. However, this study design cannot distinguish the contribution of lifestyle counseling from natural variability. Prospective controlled studies with larger cohorts, HLA stratification and longer follow-up are needed to determine whether lifestyle interventions can independently alter autoantibody dynamics and delay T1D progression.