Background/Objectives: A case-control study was conducted to determine the association of the −238 G>A and −308 G>A TNF-alpha (TNFA) promoter polymorphisms with mRNA and protein expression in 180 Systemic Lupus Erythematosus (SLE) patients and 186 control subjects (CS) from western Mexico. Methods: Genotyping was performed using the PCR-RFLP method. TNFA mRNA expression was assessed by real-time quantitative PCR, and soluble TNF-α (sTNF-α) levels were quantified by ELISA. For comparison groups, Chi-square, Mann–Whitney U, or Kruskal–Wallis tests were used. Spearman’s rank correlation coefficient determined the correlation between variables. The Area Under the Curve was used to determine the diagnosing performance of sTNF-α. Results: No differences were found in the genotype distribution of −238 G>A and −308 G>A TNFA polymorphisms between SLE patients and CS. However, the −238A allele was associated with increased SLE susceptibility (OR 1.18 CI 95% 1.02–3.50, p = 0.037). Also, logistic regression analysis showed that LN risk was significantly higher in carriers of the −308A allele (OR 3.11 IC95% 1.15–6.43; p = 0.002). On the other hand, the TNFA mRNA expression was 3.3-fold higher in SLE compared to CS. SLE patients with −308 GG genotype showed higher TNFA mRNA expression compared to GA+AA genotype carriers (p < 0.01). Regarding sTNFa levels, SLE patients showed higher concentration than CS, mainly in lupus nephritis (LN), with a weak negative correlation with estimated Glomerular Filtration Rate and an acceptable accuracy for diagnosing SLE and LN, with areas under the curve of 0.61 and 0.65, respectively. Conclusions: The −238 A allele and −308 A allele of the TNFA gene are linked to a higher risk of susceptibility to SLE and LN in the western Mexican population. Additionally, SLE patients exhibited increased TNF-alpha gene expression and sTNF-α, particularly in LN, demonstrating acceptable diagnostic performance.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and diverse tissue and organ inflammatory affections. Interleukin 21 (IL-21) is implicated in B cell survival, proliferation, differentiation, class switching, and immunoglobulin production; therefore, it is considered a key cytokine in the pathogenesis of SLE. However, its association with disease activity and clinical phenotypes remains unclear. We aimed to evaluate the association of IL-21 levels with the disease activity and clinical phenotypes in patients with SLE. Also, we analyzed the IL21 polymorphisms associated with increased IL-21 levels. Methods: The IL-21 serum levels were determined using the enzyme-linked immunosorbent assay (ELISA) method. The rs2221903 and rs2055979 polymorphisms were assessed in 300 healthy controls (HCs) and 300 patients with SLE by the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) technique. The levels of IL-21 were monitored during follow-up visits in 59 patients with SLE. Results: The patients with SLE showed higher IL-21 levels compared to the HCs. The IL-21 levels did not correlate with Mex-SLEDAI and were not different in patients with inactive, mild–moderate, and severe disease. The IL-21 levels were increased in patients with hematological affection. The ROC curve analysis revealed that the IL-21 levels had good predictive power in discriminating among patients with SLE and HCs. In a follow-up analysis, the levels of IL-21 remained higher in the patients with SLE even when the patients were in remission. Also, the rs2221903 polymorphism was associated with increased IL-21 levels. Conclusions: This study highlights the importance of IL-21 as a key cytokine in SLE. IL-21 levels are higher in patients with SLE and remain increased regardless of disease activity. According to the ROC analysis, IL-21 is a potential biomarker of SLE. Further longitudinal studies are needed to explore the relationship between IL-21 and the clinical phenotypes of SLE.

Sjögren’s disease (SjD) is an autoimmune condition marked by exocrine gland damage, lymphocytic infiltration, and autoantibody production. Recently, extrafollicular B cells have been implicated in autoimmune diseases, yet their specific role and characteristics within SjD remain largely unknown. Therefore, we aim to evaluate the distribution of atypical memory B cells (aMBCs) in patients with SjD and correlate them with clinical features. Forty SjD patients and 34 healthy subjects (HS) were included. Identification of aMBCs (CXCR5 ⁻ CD11c ⁺ ) subsets was performed, then expression of CD21 and CD38 were assessed in aMBCs subpopulations. SjD patients exhibited a systemic expansion of extrafollicular B cells, including aNAV, DP NAV, and DN2, DN3, and DN4 populations ( P < 0.001). ANCOVA revealed that DN2 expansion is uniquely independent of chronological aging ( P = 0.006). Analyzed CD19 ⁺ B cells using high-dimensional t-SNE and biaxial gating showed that aMBCs displayed heightened CD38 expression, signaling an activated phenotype primed for plasma cell differentiation. Furthermore, inverse correlations between DP NAV and USM frequencies and clinical scores (clinESSDAI, SSDDI) suggest possible sequestration within salivary glands or functional exhaustion. This pathogenic signature, manifesting as early as the naïve stage, underscores the aNAV-DN2 axis as a central hallmark of B-cell dysregulation in SjD.

Background: Systemic lupus erythematosus (SLE) features aberrant T-B cooperation and expansion of atypical memory B cells (aMBCs) characterized by the expression of CD11c and T-bet. We investigated the relationship between IL-21/IL-21R and the activation state of cTfh and Tph, with CD11c+T-bet + B cell subsets and clinical activity. Methods: A cross-sectional study was conducted involving 40 patients with systemic lupus erythematosus (SLE) and 15 healthy subjects (HS). A multiparameter flow cytometry was used to evaluate Tph (CD4 ⁺ CXCR5 ^- PD-1 ⁺ ), cTfh (CD4 ⁺ CXCR5 ⁺ PD-1 ⁺ ), and aMBCs (CD19 ⁺ CXCR5 ^- CD11c ⁺ ) subsets and intracellular expression of IL-17A (iIL-17A), IL-21 (iIL-21), and T-bet. The disease activity was assessed using the SLEDAI-2K. Results: We found an increased frequency of cTfh PD-1 ^vh , HLA-DR ⁺ , IL-21R ⁺ , and Tph PD-1 ^vh , HLA-DR ⁺ , and iIL-21 ⁺ cells in SLE patients. The aNAV T-bet ⁺ cells were expanded in SLE patients. Activated T-cell states (iIL-21 ⁺ /IL-21R ⁺ /PD-1 ^vh /HLA-DR ⁺ ) correlated with T-bet ⁺ B cells subsets. Finally, activated cTfh/Tph and aMBCs correlated with SLEDAI-2K. Conclusions: Our findings provide new insights into the cooperative expression of IL-21/IL-21R and T-bet and their potential relationships with extrafollicular B-cell responses in SLE. These results highlight the IL-21/T-bet axis, offering potential avenues for biomarker development and targeted therapeutic intervention in SLE.

La periodontitis, una de las enfermedades bucales más comunes, es una condición inflamatoria que afecta las encías y el tejido de soporte dental. Esta inflamación crónica puede llevar a la pérdida de dientes si no se trata adecuadamente. La actividad física puede influir positivamente en la salud bucal al reducir la inflamación de las encías y el riesgo de periodontitis. Este artículo examina la relación entre la actividad física y la salud de las encías, destacando la importancia de un estilo de vida activo para mantener una sonrisa saludable.