A predictive model for premature atherosclerosis in systemic lupus erythematosus based on clinical characteristics.

OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with a significant risk of atherosclerotic cardiovascular disease, especially in the development of premature atherosclerosis. Specific prediction models for premature atherosclerosis in SLE patients are still limited. The objective of this study was to establish a predictive model for premature atherosclerosis in SLE. METHOD: The study collected clinical and laboratory data from 148 SLE patients under the age of 55, between January 2021 and June 2023. The least absolute shrinkage and selection operator logistic regression model was utilized to identify potentially relevant features. Subsequently, a nomogram was developed using multivariable logistic analysis. The performance of the nomogram was evaluated through a receiver-operating characteristic curve, calibration curve, and decision curve analysis (DCA). RESULTS: A total of 148 SLE patients who fulfilled the inclusion criteria were enrolled in the study, of whom 53 patients (35.81%) met the definition of premature atherosclerosis. Hypertension, antiphospholipid syndrome, azathioprine use, duration of glucocorticoid, and age of patients were included in the multivariable regression. The nomogram, based on the non-overfitting multivariable model, was internally validated and demonstrated sufficient clinical utility for assessing the risk of premature atherosclerosis (area under curve: 0.867). CONCLUSIONS: The comprehensive nomogram constructed in this study serves as a useful and convenient tool for evaluating the risk of premature atherosclerosis in SLE patients. It is helpful for clinicians to early identify SLE patients with premature atherosclerosis and facilitates the implementation of more effective preventive measures. Key Points • SLE patients are at a significantly higher risk of developing premature atherosclerosis compared to the general population, and this risk persists even in cases with low disease activity. Traditional models used to evaluate and predict premature atherosclerosis in SLE patients often underestimate the risk. • This study establishes a comprehensive and visually orientated predictive model of premature atherosclerosis in SLE patients, based on clinical characteristics. • The scoring system allows for convenient and effective prediction of individual incidence of premature atherosclerosis, and could provide valuable information for identification and making further intervention decision.

Prognostic factors in patients with secondary hemophagocytic lymphohistioc ytosis in a Chinese cohort.

Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome with high mortality mediated by an unbridled and persistent activation of cytotoxic T lymphocytes and natural killer cells. However, the influence factors of early death in adult sHLH patients are still not fully elucidated, which need further investigating. We have conducted an observational study of adult HLH patients between January 2016 and December 2022. All patients are enrolled according to HLH-2004 criteria. Clinical manifestations, laboratory data, treatments, and outcomes have been recorded. Influence factors associated with prognosis are calculated by using logistic regression models. Overall, 220 patients enrolled in this study. The etiologies of HLH were divided into five groups including autoimmune-associated hemophagocytic syndrome (AAHS) (n = 90, 40.9%), malignancies (n = 73, 33.2%), EBV-HLH (n = 18, 8.2%), infection excluded EBV (n = 24, 10.9%), and other triggers (n = 15, 6.8%). Among them, EBV-HLH had the highest mortality (77.8%), and AAHS had the lowest mortality (14.4%). Multivariate analysis indicated that age (≥ 38 years old), cytopenia ≥ 2 lines, platelets (≤ 50 × 109/L), aspartate aminotransferase (≥ 135U/L), prothrombin time (≥ 14.9 s) and activated partial thromboplastin time (≥ 38.5s), EBV, and fungal infection are independent risk factors for poor prognosis of HLH. Adult HLH patients with elder age, cytopenia ≥ 2 lines, levels of decreased platelets, increased AST, prolonged PT and APTT, EBV, and fungal infection tend to have a poor prognosis.

Tyro3 receptor tyrosine kinase contributes to pathogenic phenotypes of fibroblast-like synoviocytes in rheumatoid arthritis and disturbs immune cell balance in experimental arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by synovitis and joint damage, the underlying causes of which remain unclear. Our prior investigations revealed a notable correlation between the expression of Tyro3 Protein Tyrosine Kinase (Tyro3TK) and the progression of RA. To further elucidate the pathogenic role of Tyro3TK in RA, we analyzed the influence of Tyro3TK on pathogenic phenotypes of RA fibroblast like synoviocyte (FLS) in vitro and compared disease severity, joint damages and immunological parameters of K/BxN serum transfer arthritis (STA) in Tyro3TK-/- deficient mice and wild type controls. Our findings underscored the remarkable effectiveness of Tyro3TK blockade, as evidenced by diminished secretion of inflammatory cytokines and matrix metalloproteinases (MMPs), curtailed migration and invasiveness of RAFLS, and attenuated differentiation of pathogenic helper T cell subsets mediated by RAFLS. Correspondingly, our in vivo investigations illuminated the more favorable outcomes in Tyro3TK-deficient mice, characterized by reduced joint pathology, tempered synovial inflammation, and restored immune cell equilibrium. These data suggested that Tyro3TK might contribute to aggravated autoimmune arthritis and immunological pathology and act as a potential therapeutic target for RA.

Serum IgA levels for predicting the development of rapidly progressive interstitial lung disease in dermatomyositis.

BACKGROUND: Some patients with dermatomyositis (DM) can develop rapidly progressive interstitial lung disease (RPILD) that is resistant to treatment and life-threatening. Convenient and practical predictive factors for the development of RPILD are currently lacking. We aimed to identify independent risk factors for RPILD in patients with DM. METHODS: A total of 71 patients with DM admitted to our hospital between July 2018 and July 2022 were retrospectively reviewed. Risk factors to predict RPILD were identified by univariate and multivariate regression analyses, and significant variates for RPILD were included to establish a risk model. RESULTS: Multivariate regression analysis revealed that the risk of RPILD was significantly associated with serum IgA levels. The area under the risk model curve, established by IgA levels combined with other independent predictors including the anti-melanoma differentiation-associated gene 5 (MDA5) antibody, fever, and C-reactive protein, was 0.935 (P < 0.001). CONCLUSION: A higher serum IgA level was identified as an independent risk factor for RPILD in patients with DM.

Elevated serum free IL-18 in neuropsychiatric systemic lupus erythematosus patients with seizure disorders.

BACKGROUND: Since dysregulation of total Interleukin (IL)-18 and IL-18 binding protein (IL-18BP) may participate in systemic lupus erythematosus (SLE) and contribute to the occurrence of non-autoimmune epilepsy, the aim of the current work is to investigate whether the interaction between IL-18 and IL-18BP plays any role in neuropsychiatric systemic lupus erythematosus related seizures. METHODS: Data from 137 SLE patients and 30 healthy controls (HC) were consecutively collected from 2020 to 2021. Serum levels of total IL-18 and IL-18BP for all patients and HC were measured by ELISA test. Free IL-18 was calculated based on the law of mass action. RESULTS: Among the 137 SLE patients, 103 had active disease and were classified into NPSLE (n = 50) and Non-NPSLE (n = 53) groups. Among the NPSLE patients, 16 had seizure disorders. Serum free IL-18 levels were increased in NPSLE (277.6 [150.9-428.8]pg/mL) and were correlated with disease activity (r = 0.268, p = 0.002). Moreover, serum free IL-18 levels in NPSLE patients with seizure disorders (350.9 [237.9-455.9]pg/mL) were significantly higher than the levels in those with other neuropsychiatric symptoms (237.7 [124.6-428.8] pg/mL). CONCLUSIONS: The expression of free IL-18 was increased in neuropsychiatric systemic lupus erythematosus(NPSLE), especially in NPSLE related seizures. Also, serum levels of free IL-18 were significantly increased in active SLE patients. In this regard, free IL-18 may be involved in the pathogenesis of NPSLE related seizures and associated with disease activity.

Identification of Circular RNAs Circ_0005008 and Circ_0005198 in Plasma as Novel Biomarkers for New-Onset Rheumatoid Arthritis.

The progression of autoimmune diseases is affected by the differential expression of circular RNAs (circRNAs). However, in the plasma from rheumatoid arthritis (RA), circRNAs have an uncertain role. Herein, microarray analysis was used to determine the plasma expression profile of circRNAs from new-onset patients with RA and healthy controls (HCs). CircRNA expression was verified using quantitative real-time reverse transcription PCR. The correlation between clinical variables and circRNA expression was assessed using Spearman's correlation test. The diagnostic value of plasma circRNAs was evaluated using receiver operating characteristic (ROC) curves. Circ_0005008 and circ_0005198 were confirmed to be elevated significantly in plasma samples from new-onset patients with RA compared with those from HCs and from patients with systemic lupus erythematosus. Among these new-onset patients with RA, we found that the levels of circ_0005008 and circ_0005198 correlated positively with the severity of disease, including the rheumatoid factor, C-reactive protein, the erythrocyte sedimentation rate, and the disease activity score in 28 joints (DAS28). However, their expression levels did not correlate with anti-cyclic citrullinated peptide antibodies. Analysis using ROC curves implied that circ_0005008 and circ_0005198 have significant value in the diagnosis of RA. In addition, we found that compared with that in osteoarthritis fibroblast-like synoviocytes (OA-FLSs), circ_0005198 expression was enhanced in RA-FLSs and correlated positively with DAS28. The level of the miRNA target of circ_0005198, miR-4778-3p, was identified as significantly decreased in RA-FLSs, and the expression levels of circ_0005198 and miR-4778-3p correlated significantly and negatively. The results suggested that in new-onset patients with RA, plasma circ_0005008 and circ_0005198 levels are associated with disease activity and represent possible RA biomarkers.

Circ_0088194 Promotes the Invasion and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes via the miR-766-3p/MMP2 Axis.

Dysregulation of circular RNAs (circRNAs) is involved in various human diseases. Fibroblast-like synoviocytes (FLSs), which form the lining of the joint, are epigenetically imprinted with an aggressive phenotype and contribute to joint destruction in rheumatoid arthritis (RA). In the present study, we identified a novel circRNA, Circ_0088194, which was upregulated in RA fibroblast-like synoviocytes (RA-FLSs) and correlated with the disease activity score in 28 joints. Overexpression of Circ_0088194 promoted RA-FLS migration and invasion, while inhibition of Circ_0088194 had the opposite effect. Mechanistically, Circ_0088194 acted as a miR-766-3p sponge to relieve the repressive effect of miR-766-3p on its target, MMP2 (encoding matrix metalloproteinase 2), thereby promoting migration and invasion. The expression level of Circ_0088194 was inversely correlated with that of miR-766-3p in RA-FLSs. Importantly, overexpression of miR-766-3p partially blocked the migration and invasion induced by Circ_0088194 overexpression. Collectively, this study identified a novel circRNA Circ_0088194 that promotes RA-FLS invasion and migration via the miR-766-3p/MMP2 axis. Circ_0088194 might represent a novel therapeutic target to prevent and treat RA.