Systemic lupus erythematosus (SLE) is an autoimmune illness marked by the loss of immune tolerance and the production of autoantibodies against nucleic acids and other nuclear antigens (Ags). B lymphocytes are important in the immunopathogenesis of SLE. Multiple receptors control abnormal B-cell activation in SLE patients, including intrinsic Toll-like receptors (TLRs), B-cell receptors (BCRs), and cytokine receptors. The role of TLRs, notably TLR7 and TLR9, in the pathophysiology of SLE has been extensively explored in recent years. When endogenous or exogenous nucleic acid ligands are recognized by BCRs and internalized into B cells, they bind TLR7 or TLR9 to activate related signalling pathways and thus govern the proliferation and differentiation of B cells. Surprisingly, TLR7 and TLR9 appear to play opposing roles in SLE B cells, and the interaction between them is still poorly understood. In addition, other cells can enhance TLR signalling in B cells of SLE patients by releasing cytokines that accelerate the differentiation of B cells into plasma cells. Therefore, the delineation of how TLR7 and TLR9 regulate the abnormal activation of B cells in SLE may aid the understanding of the mechanisms of SLE and provide directions for TLR-targeted therapies for SLE.

We to measure the serum levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in patients diagnosed with connective tissue disease (CTD)-associated pulmonary arterial hypertension (PAH) (CTD-PAH) and to analyze their clinical implications. Thirty patients who were diagnosed with CTD-PAH via right heart catheterization (RHC) were enrolled in the observation group. Additionally, twenty CTD patients without PAH (CTD-non-PAH) were enrolled in the CTD-non-PAH group, and twenty healthy participants were enrolled in the healthy control group. Additional data on CTD-PAH patients, including demographic characteristics, laboratory parameters, and hemodynamic measurements, were obtained. The serum levels of HIF-1α and VEGF in all participants were measured using an enzyme-linked immunosorbent assay (ELISA). Pearson correlation was utilized to determine the correlation between the expression levels of these factors and clinical data. Receiver operating characteristic (ROC) curves were constructed, and the area under the curve (AUC) was calculated to evaluate the diagnostic efficacy of expression of HIF-1α and VEGF for diagnosing CTD-PAH. Participants in the three groups were age-matched. The CTD-PAH group included 29 females and 1 male, and systemic lupus erythematosus (SLE) was the most prevalent CTD diagnosis (17/30). Serum levels of VEGF and HIF-1α were significantly greater in both CTD-PAH and CTD-non-PAH patients compared to the healthy controls (P < 0.01). In addition, the serum concentration of HIF-1α in the CTD-PAH group was significantly greater than that in the CTD-non-PAH group (248.86 ± 18.85 and 224.64 ± 12.22, respectively, P = 0.0022). Similarly, the serum concentration of VEGF in the CTD-PAH group was significantly greater than that in the CTD-non-PAH group (251.11 ± 48.37 and 222.120 ± 18.57, respectively, P = 0.0026). In patients with CTD-PAH, the concentrations of HIF-1α and VEGF are significantly positively correlated with mPAP (r = 0.81, r = 0.88). Both HIF-1α and VEGF concentrations were positively correlated with BNP levels (r = 0.5340, r = 0.6472) and negatively correlated with the 6-Minute Walk Distance (6MWD) (r=-0.46, r=-0.47, respectively, P < 0.01). When VEGF and HIF-1α were combined, the diagnostic ROC curve yielded an AUC of 0.933. Increased serum levels of HIF-1α and VEGF were observed in CTD-PAH patients compared to CTD-non-PAH patients and healthy controls, which, along with their positive correlations with mPAP and BNP levels and negative correlations with the 6MWD, indicate their potential as biomarkers for diagnosing CTD-PAH.

Introduction: Rheumatoid arthritis (RA) and Sjögren’s syndrome (SS) are systemic autoimmune conditions. SS frequently occurs associated with RA. In patients with RA, those with SS exhibit a higher disease burden, increased disease activity, and more complex comorbidities compared with those without SS.Case report: We report a 54-year-old female patient who was previously diagnosed with early-stage RA less than 1 year ago. She was subsequently confirmed to have SS associated with RA. Additionally, she developed multiple autoimmune comorbidities, including autoimmune hepatitis and type 1 renal tubular acidosis. The patient resisted various treatments, including immunosuppressive drugs, disease-modifying antirheumatic drugs, and anti-inflammatory small-molecule drugs. This was evidenced by poor DA28 responses, persistent laboratory abnormalities, and ongoing symptoms and signs. Finally, she responded well to Telitacicept, a BLyS/APRIL dual inhibitor.Discussion: Even in the early stage, multiple autoimmune comorbidities can exhibit high levels of disease activity and may not respond to conventional therapies. Telitacicept, the first dual inhibitor of BLyS/APRIL, has the potential to provide significant efficacy and safety for RA patients who also have overlapping SS and other autoimmune diseases that do not respond to standard treatments. The limitations included the absence of a liver biopsy and the short follow-up period.

Background: Variations in the TLR9 gene have been associated with several autoimmune disorders, but the relationship between TLR9 polymorphisms and systemic lupus erythematosus (SLE) remains controversial. This study aims to evaluate the potential association between three single-nucleotide polymorphisms (SNPs) within the TLR9 gene and susceptibility to SLE in the Han Chinese female population. Methods: A total of 150 SLE patients and 151 healthy controls of Han Chinese ethnicity were enrolled. Genotyping of TLR9 was performed using sequence-specific primer (SSP) polymerase chain reaction and validated by Sanger sequencing. Associations between the SNPs and SLE susceptibility were analyzed using the chi-square test or Fisher’s exact test. Additionally, correlations between the SNPs and clinical manifestations of SLE were assessed. Results: The TLR9 rs352139 polymorphism was significantly associated with increased SLE susceptibility in heterozygous (AG vs. AA, OR = 1.79, 95% CI [1.07–2.99], p = 0.025), homozygous (GG vs. AA, OR = 2.11, 95% CI [1.06–4.19], p = 0.033), dominant (GG+AG vs. AA, OR = 1.86, 95% CI [1.15–3.03], p = 0.012), and allele (G vs. A, OR = 1.49, 95% CI [1.07–2.06], p = 0.017) models. Similarly, rs352140 was significantly associated with SLE risk in homozygous (TT vs. CC, OR = 2.47, 95% CI [1.23–4.96], p = 0.010), recessive (TT vs. CC+CT, OR = 2.57, 95% CI [1.35–4.88], p = 0.003), and allele (T vs. C, OR = 1.43, 95% CI [1.03–1.99], p = 0.031) models. Haplotype analysis revealed that haplotype HT1 (C/A/T) had a protective effect against SLE (OR = 0.70, 95% CI [0.506–0.966], p = 0.030), while haplotype HT2 (T/G/T) was positively associated with increased susceptibility (OR = 1.505, 95% CI [1.068–2.121], p = 0.019). Conclusions: These findings suggest that the TLR9 rs352139 and rs352140 polymorphisms are significantly associated with increased susceptibility to SLE in the Han Chinese population, indicating a potential role of TLR9 in the pathogenesis of SLE.

FOXP3 is a transcription factor that regulates the development and function of Treg, playing an essential role in preventing autoimmune diseases. Variation in FOXP3 can impair the function of Treg cells, thus destroying their inhibitory capacity and leading to autoimmune diseases. This paper investigated whether the three SNPs in the FOXP3 gene (-3279 C/A, -924 A/G and -6054 del/ATT) are associated with systemic lupus erythematosus (SLE) susceptibility in the Han Chinese population. The study cohort comprised 122 SLE patients and 268 healthy controls. Genotyping was performed by polymerase chain reaction sequence-specific primer (PCR-SSP). Furthermore, we examined the potential clinical manifestations associated with FOXP3 polymorphisms in SLE patients. The results showed that the -3279 (C > A) was significantly associated with the SLE risk in a homozygote (OR = 3.24, 95% CI = 1.23-8.52, p = .013, AA vs. CC), dominant (OR = 1.68, 95% CI = 1.07-2.65, p = .025, AC + AA vs. CC), recessive (OR = 2.90, 95% CI = 1.12-7.55, p = .023, AA vs. AC + CC) and allelic (OR = 1.72, 95% CI = 1.18-2.53, p = .005, A vs. C) models. In addition, -924 (A > G) was positively associated with SLE risk in the heterozygote (OR = 1.66, 95% CI = 1.04-2.66, p = .033, AG vs. AA) and dominant (OR = 1.59, 95% CI = 1.01-2.49, p = .042, AG + GG vs. AA) models, whereas -6054 (del > ATT) was not associated with SLE. Moreover, the immunological index analysis suggested that decreased complement C4 occurred more frequently in SLE patients carrying the minor allele (A) -3279 (C > A) than those not (p = .005). We demonstrated that -3279 (C > A) and -924 (A > G) were associated with an increased risk of SLE and the immunological index, indicating that the FOXP3 variation is potentially related to the occurrence and development of SLE.