Correlation Between B-Cell Activating Factor of the Tumor Necrosis Factor Family Level in Serum and Immune Inflammation in Patients with Neuropsychiatric Systemic Lupus Erythematosus and its Clinical Value.

OBJECTIVE: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a form of SLE associated with severe NP syndromes causing mortality and morbidity. Respecting the fundamental of BAFF in NPSLE pathophysiology, we investigated its clinical value. METHODS: Totally 105 NPSLE and 101 SLE cases without NPSLE (non-NPSLE, control) were included. Serum BAFF/TNF-α/IL-6/IL-10 levels were measured using ELISA kits. T lymphocytes were detected by flow cytometry. The independent influencing factors for NPSLE, and the auxiliary diagnostic efficacy and the ability of BAFF levels to predict adverse prognosis of NPSLE patients were analyzed by multiple factor logistic regression, and ROC curve and survival curve. RESULTS: In NPSLE patients, serum BAFF level was increased and positively correlated with SLEDAI-2k, serum proinflammatory cytokines, while negatively correlated with CD4+T/CD8+T cells, and anti-inflammatory cytokine. High serum BAFF protein level was associated with a higher risk of developing NPSLE. The AUC of serum BAFF > 301.7 assisting in NPSLE diagnosis was 0.8196. Furthermore, high levels of serum BAFF were associated with a higher risk of adverse outcomes in NPSLE patients. . CONCLUSION: Serum BAFF level in NPSLE patients was correlated with lymphocytes and high serum BAFF protein level could assist in diagnosis and to predict adverse outcomes in NPSLE patients.

Increased frequency of circulating follicular helper T cells in lupus patients is associated with autoantibody production in a CD40L-dependent manner.

This study was to determine the frequency of circulating follicular helper T (Tfh) cells in patients with systemic lupus erythematosus (SLE) and investigate the relationship between Tfh cells and autoantibody production. An increased frequency of circulating Tfh cells was found in SLE patients, and there were positive co-relationship between Tfh cells and SLEDAI, serum IgG, Anti-nuclear antibody titers and anti-dsDNA (P=0.0004, 0.0006, 0.0237, 0.0000, respectively). B cells sorted from SLE patients produced more IgG than healthy controls in the presence of autologous CD4(+) T cells. CD4(+) T cells were further sorted into CXCR5(+) and CXCR5(-) cells, and CD4(+)CXCR5(+) T cells helped B cells producing more IgG than CD4(+)CXCR5(-) T cells. Blocking the interaction of T cells and B cells by anti-CD40L but not anti-ICOSL dramatically decreased antibody production in the co-culture system. This study suggests that increased frequency of circulating Tfh cells in SLE patients is associated with excess B-cell help and autoantibody production in a CD40L dependent manner.

Imbalance of peripheral blood Th17/Treg increases neutrophil-to-lymphocyte ratio in patients with dermatomyositis.

OBJECTIVE: To explore and analyze the association between peripheral blood Th17/Treg balance and neutrophil-to-lymphocyte ratio (NLR) in patients with dermatomyositis (DM). METHODS: Data of 83 DM patients hospitalized between January 2020 to April 2022 were collected, including 43 patients in the active phase (DM active-phase group) and 40 in the remission phase (DM remission-phase group). Additionally, data of 50 healthy subjects who underwent physical examinations and immunologic function testing in the same period were taken as a control group. We detected the percentage of Th17 and Treg cells by flow cytometry, calculated patient's NLR and laboratory test indicators, and analyzed the correlation of Th17/Treg balance with NLR and laboratory indicators. RESULTS: Th17 percentage and Th7/Treg ratio in the DM active-phase group were higher than those in the DM remission-phase group (P<0.05), while Treg percentage was lower in the active-phase group than in the remission-phase group (P<0.05). The creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), erythrocyte deposition rate (ESR), and NLR in DM patients were significantly higher than those of the control group (P<0.05), and were associated with the disease activity of DM. The ratio of Th17/Treg was positively correlated with CK, LDH, AST, ALT, ESR, and NLR (P<0.05). NLR was positively correlated with CK, LDH, AST, ALT, and ESR (P<0.05). CONCLUSION: DM patients exhibit changes in immune balance of Th17/Treg and an increase in the NLR. The Th17/Treg ratio in the patients is closely associated with the NLR, which suggests that the immune balance mechanism may interact with the inflammatory response of the body, collectively contributing to the progression of DM.

Hsa_circ_0007707 participates in PDE3B-mediated apoptosis inhibition and inflammation promotion in fibroblast-like synoviocytes.

Synovial samples collected from 30 rheumatoid arthritis (RA) patients and 30 normal controls were used to isolate fibroblast-like synoviocytes (FLSs) and named FLS-RA and FLS-Normal, respectively. Real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to detect circ_0007707 expression. Effects of circ_0007707 silencing on cell proliferation and apoptosis were evaluated using cell counting kit-8, 5-ethynyl-2'-deoxyuridine (Edu), and flow cytometry assays. Levels of pro-inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Increased circ_0007707 expression was observed in synovial samples from RA patients and FLS-RA cells. Functional analysis showed circ_0007707 silencing restrained cell proliferation, induced cell apoptosis, and decreased cell inflammatory response in FLS-RA cells. Mechanistic analysis revealed the sponge function of circ_0007707 on miR-27b-3p, and miR-27b-3p inhibition weakened circ_0007707 knockdown-mediated effects on FLS-RA cell proliferation, apoptosis, and inflammatory response. Circ_0007707 could mediate PDE3B expression via sponging miR-27b-3p, and PDE3B overturned miR-27b-3p mimic-mediated effects on FLS-RA cell proliferation, apoptosis, and inflammatory response. Circ_0007707 mediated cell apoptosis and inflammatory response in FLS-RA cells through the miR-27b-3p/PDE3B axis, indicating the potential function of circ_0007707 as a target for RA treatment.

Pirfenidone inhibits cell fibrosis in connective tissue disease-associated interstitial lung disease by targeting the TNF-α/STAT3/KL6 pathway.

Background: To explore the effect and mechanism of pirfenidone in inhibiting pulmonary fibrosis in connective tissue disease-associated interstitial lung disease (CTD-ILD). Methods: From 2018 to 2020, 50 CTD-ILD patients were enrolled in the clinical study. Based on whether pirfenidone was used during treatment, patients were enrolled into the pirfenidone group and the control group. Pulmonary function tests were compared before and after treatment. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the expression of tumor necrosis factor-α (TNF-α), signal transducer and activator of transcription 3 (STAT3), and Krebs Von den Lungen-6 (KL-6) in venous blood before and after treatment. Rat type II (RLE-6TN) lung epithelial cells were cultivated for in vitro experiments, and they were sorted into the control group, bleomycin group, pirfenidone group, TNF-α group, Stattic group, and TNF-α/Stattic combined treatment group. For the in vitro experiments, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests were used to evaluate cell proliferation, Reverse Transcription-Polymerase Chain Reaction(RT-PCR) was performed to detect STAT3 and KL-6 mRNA expression levels, ELISA was utilized to detect TNF-α and E-cadherin expression levels, and Western blotting (WB) was performed to determine α-smooth muscle actin (α-SMA), vimentin, TNF-α, STAT3, phosphorylated signal transducer and activator of transcription 3 (PSTAT3) and KL-6 expression. Results: In the clinical study, the pulmonary function indices including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF) and partial pressure (PaO2) of the patients in the study group were superior to those in the control group (P<0.05). The serum TNF-α, STAT3 and KL-6 levels in the study group were significantly lower than those in the control group (P<0.05). In the in vitro experiments, the α-SMA, vimentin, STAT3 and KL-6 levels in the treatment group were significantly lower than those in the bleomycin group (P<0.05). Compared with those in the pirfenidone group, the α-SMA, vimentin, STAT3 and KL-6 levels in the TNF-α-treated group were significantly upregulated (P<0.05). Meanwhile, cell viability was further upregulated (P<0.05), and the expression of STAT3 and KL-6 was further decreased in the Stattic-treated group (P<0.05). In the group treated with infliximab combined with Stattic, TNF-α expression was significantly increased (P<0.05), cell activity was significantly restored (P<0.05), and the STAT3, KL-6 and E-cadherin expression levels were inhibited (P<0.05). Conclusions: Pirfenidone improved pulmonary function 1 and decreased TNF-α, STAT3, and KL-6 expression in CTD-ILD patients. Moreover, pirfenidone inhibits cell fibrosis through the TNF-α/STAT3/Mucin 1(MUC1) pathway.