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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. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is a disorder with a complex immunopathogenesis. It is well known that the disease begins with immunological alterations and autoantibody appearance in the serum years before clinical onset. As SLE has a strong tendency to familial aggregation, first‐degree relatives (FDRs) constitute a group at elevated risk. The current understanding is that external risk factors trigger underlying immune dysregulations, leading to overt disease in those with elevated genetic risk. Objective: This cross‐sectional study investigates the degree to which clinical features, external risk factors, and immunological profiles differ in SLE FDRs from healthy individuals and SLE patientts. Methods: Three groups were studied: Lupus patient FDRs (n = 56), healthy controls (n = 20), and SLE patients (n = 20). FDRs and healthy participants completed a detailed clinical questionnaire that included questions regarding smoking and estrogen drug history. All participants were tested for the presence of the following antinuclear autoantibodies (ANAs) against: nRNP/Sm, Sm, Ro60, Ro‐52, La, Scl‐70, PM‐Scl, PM‐ Scl, Jo‐1, CENP B, PCNA, dsDNA, nucleosomes, histones, RibP, AMA M2, DFS70, and eight soluble cytokines, including transforming growth factor‐β (TGF‐β), vitamin D levels, and antibodies against Epstein‐Barr virus (EBV). Results: Compared with the healthy controls, FDRs had higher titers of ANA, more specific staining immunofluorescent patterns, and more autoantibody specificities. Furthermore, FDRs differed significantly in their TGF‐β levels from the other two groups. In FDRs, some clinical features (hair loss, skin, and oral ulcer‐like lesions) were associated with higher ANA titers and some (oral ulcer‐like lesions) with the anti‐Ro60‐specific antibody. Interestingly, there was an association between ANA titers and levels of antibodies against EBV only in the FDR group. Conclusion: First‐degree relatives display unique clinical and immunological profiles, placing them between healthy individuals and SLE patients, with a balance between compensated immune dysregulation and disease‐developing potential. A possible association between ANA titer and the number of clinical complaints is observed, which needs to be confirmed in more extensive studies. [ABSTRACT FROM AUTHOR]