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Chronic inflammation is believed as the main culprit of the link between cardiovascular disease (CVD) and rheumatoid arthritis (RA). Interleukin‐6 (IL‐6) is a pro‐inflammatory cytokine with a key role in RA pathophysiology and also correlates with joint destruction and disease activity. This study evaluates the association between IL‐6 plasma level and cardiac biomarker NT‐proBNP, HS‐CRP, CVD predictor algorithms, Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE), as well as with CXCL9 and its receptor, CXCR3 in RA patients compared to the controls. Sixty RA patients (30 early and 30 late) and 30 healthy persons were included in this study. IL‐6 and NT‐proBNP plasma levels were measured by the ELISA. Also, HS‐CRP plasma levels were quantified using the immunoturbidimetric assay. The CVD risk was assessed by the FRS and SCORE. IL‐6 plasma levels were significantly higher in the early and late RA patients compared to the controls (p < 0.001). There was a positive correlation between IL‐6 with DAS‐28 (p = 0.007, r = 0.346), BPS (p = 0.002, r = 0.396), BPD (p = 0.046, r = 0.259), SCORE (p < 0.001, r = 0.472), and FRS (p < 0.001, r = 0.553), and a negative association with HDL (p = 0.037, r = −0.270), in the patients. Also, IL‐6 plasma level positively correlated with HS‐CRP (p = 0.021, r = 0.297) and NT‐proBNP (p = 0.045, r = 0.260) in the patients. Furthermore, a positive association was found between IL‐6 plasma levels and CXCL9 (p = 0.002, r = 0.386), and CXCR3 (p = 0.018, r = 0.304) in the patients. Given the interesting association between IL‐6 with various variables of CVD, IL‐6 may be considered a biomarker for assessing the risk for future cardiovascular events in RA patients. [ABSTRACT FROM AUTHOR]

Purpose: Solid organ transplant recipients (SOTR) have a high risk for severe COVID-19 infection; hence it is necessary to find alternative treatment strategies to protect these patients from the complications caused by the severe progression of the disease. This study aimed to determine the effectiveness of sotrovimab among SOTR with COVID-19. Materials and methods: A systematic literature search was conducted with relevant keywords to find studies that reported clinical outcomes regarding sotrovimab administration in SOTR outpatients with confirmed COVID-19 infection, who had mild-to-moderate symptoms. Results: Of 796 records found by a systematic search, only 14 met the inclusion criteria for reporting in a systematic review and only 6 enrolled in a meta-analysis. This meta-analysis indicated that SOTR outpatients with mild to moderate COVID-19 who received sotrovimab had lower likelihood of all-cause hospitalization (OR: 0.29, CI: 0.16, 0.52, p < 0.001), ICU admission (OR: 0.17, CI: 0.05, 0.64, p = 0.009) and mortality (OR: 0.15, CI: 0.03, 0.64, p = 0.010) within 30 days of drug infusion compared to controls. Conclusions: Our findings confirm that monoclonal antibody therapy with sotrovimab in SOTR is associated with better outcomes and consequently a reduced risk of disease progression in this high-risk population. [ABSTRACT FROM AUTHOR]

Autoantibodies (AABs) play a critical role in the pathogenesis of autoimmune diseases (AIDs) and serve as a diagnostic and prognostic tool in assessing these complex disorders. Viral infections have long been recognized as a principal environmental factor affecting the production of AABs and the development of autoimmunity. COVID‐19 has primarily been considered a hyperinflammatory syndrome triggered by a cytokine storm. In the following, the role of maladaptive B cell response and AABs became more apparent in COVID‐19 pathogenesis. The current review will primarily focus on the role of extrafollicular B cell response, Toll‐like receptor‐7 (TLR‐7) activation, and neutrophil extracellular traps (NETs) formation in the development of AABs following SARS‐CoV‐2 infection. In the following, this review will clarify how these AABs dysregulate immune response to SARS‐CoV‐2 by disrupting cytokine function and triggering neutrophil hyper‐reactivity. Finally, the pathologic effects of these AABs will be further described in COVID‐19 associate clinical manifestations, including venous and arterial thrombosis, a multisystem inflammatory syndrome in children (MIS‐C), acute respiratory distress syndrome (ARDS), and recently described post‐acute sequelae of COVID‐19 (PASC) or long‐COVID. [ABSTRACT FROM AUTHOR]

Fibroblast-like synoviocytes (FLSs), the main pathological cells in rheumatoid arthritis (RA), display tumor-like phenotype, including hyper-proliferation, apoptosis resistance, and aggressive phenotype. Excessive proliferation and insufficient apoptosis of RA-FLSs can lead to hyperplastic synovial pannus tissue, excess production of inflammatory mediators, and destruction of joints. In this article, we investigate the effect of PRIMA-1MET on the apoptosis induction and inhibition of pro-inflammatory cytokines in RA-FLSs. Synovial tissue samples were obtained from 10 patients with RA. The FLSs were treated with different concentrations of PRIMA-1MET. The rate of apoptosis and cell survival was assessed by flow cytometry and MTT assay and Real-time quantitative PCR was performed to evaluate the transcription of p53, IL-6, IL-1β, TNF-α, Noxa, p21, PUMA, Bax, Survivin, and XIAP in treated RA-FLSs. The protein level of p53, IκBα, and phospho-IκBα were measured using Western blotting. The results showed that PRIMA-1MET induced apoptosis in RA-FLSs and increased significantly the expression of Noxa, and decreased significantly IL-6, IL-1β, p53, and phospho-IκBα expression. PRIMA-1MET can induce apoptosis in RA-FLSs through induction of Noxa expression while p53 was downregulated. Furthermore, PRIMA-1MET treatment results in the suppression of pro-inflammatory cytokine production and NF-κB inhibition. Given the role of p53 and NF-κB in RA-FLSs, PRIMA-1MET can be considered as a new therapeutic strategy for rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoinflammatory and self-perpetuating disease with both articular and extra-articular manifestations, such as cardiovascular complications, which are the leading cause of mortality and morbidity in RA patients. Impaired sugar and lipid metabolism are considered as the critical risk factors for cardiovascular disease (CVD). Regarding the regulatory function of Raptor in the immunometabolism, in this study, we evaluated the association between plasma sugar and lipid profiles with the gene expression of Raptor and the cytokine tumor necrosis factor-α (TNF-α), as an inflammatory mediator, in peripheral blood leukocyte of RA patients. Thirty-five RA patients who received combinational disease modified anti-rheumatoid drugs (DMARD) regimen and thirty healthy subjects enrolled in this study. The gene expression of Raptor was assessed by the real-time PCR method, and the Plasma levels of glucose and lipids, as well as TNF-α, were obtained using Hitachi device and enzyme-linked immunosorbent assay (ELISA) technique, respectively. The gene expression of Raptor was reduced significantly in RA patients compared to the healthy subjects (p =.001). The plasma level of HDL was significantly higher in RA patients than the control group (p =.001), while the plasma level of LDL was reduced significantly in these patients (p =.001). In our study, the reduced gene expression of Raptor may contribute to the impaired immunometabolism in RA patients, which is independent of plasma sugar and lipid profile. [ABSTRACT FROM AUTHOR]

Background: The effect of obesity on disease severity in rheumatoid arthritis (RA) remains controversial. Adipocytes secrete pro-inflammatory cytokines and adipokines which may contribute to RA disease activity. The goal of the present study is to address the association between body mass index (BMI) with plasma levels of leptin, pro-inflammatory cytokines, and RA disease severity. Methods: Fifty RA patients (20 newly diagnosed and 30 under treatment) as well as 30 age- and sex-matched healthy subjects were included in this survey. The plasma levels of leptin and pro-inflammatory cytokines, including TNF-α and IL-6, were measured, and the results were compared among the patients in the three different categories of BMI, including <25, ≥25–30, and ≥30. Results: In our study, a significant positive correlation was observed between disease activity score-28 (DAS-28) and BMI in overweight (OW) RA patients (p =.036 r = 0.440). The plasma levels of leptin were significantly higher in patients group, compared to healthy subjects (p <.05); moreover, leptin levels were significantly higher in OW and obese patients compared to RA patients with normal BMI (p =.011, p =.001, respectively) and also BMI had positive correlation with leptin concentrations just in the newly diagnosed patients (p <.0001, r = 0.748). There was no correlation between leptin and DAS-28. The plasma IL-6 and TNF-α did not show significant differences between RA patients and healthy subjects, and also the plasma leptin did not have any correlation with plasma levels of IL-6 and TNF-α. Conclusion: BMI contribution to RA disease severity is independent of systemic levels of leptin and pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]