Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple organs. It is often called “immortal cancer” due to the difficulties in disease treatment. As the cornerstone of immune regulation, the programmed cell death protein 1 (PD-1) has been extensively studied in the context of chronic inflammation due to its ability of regulating immune response and immunosuppression. Recently, more and more studies on rheumatic immune related complications have also focused on PD-1 and proposed that the use of PD-1 agonist could inhibit the activation of lymphocytes and alleviate SLE disease activity. In this review, we summarized the role of PD-1 in SLE, implicating its potential application as a biomarker to predict SLE disease activity; we also proposed that the combination of PD-1 agonist and low-dose IL-2 may have better therapeutic efficacy, shining light on a new direction for developing specific treatment approaches.

BACKGROUND:The relationship between thyroid hormones and body anthropometric measures in type 2 diabetes mellitus (T2DM) patients with normal thyroid function is unclear. The purpose of this study was to evaluate the association between thyroid hormones and body composition in euthyroid T2DM patients in men and women. MATERIAL AND METHODS:This was a cross-sectional study that included 561 euthyroid T2DM patients. Fasting venous blood was collected to test laboratory indexes. Bioelectric impedance analysis (BIA) was used to measure body composition. Propensity score matching (PSM) was used to enroll patients with similar baseline characteristics. The least absolute shrinkage and selection operator (LASSO) algorithm was used to establish a linear regression model of thyroid hormone and body composition. PSM was performed to match 159 men and 159 women. RESULTS:The LASSO regression analysis suggested that thyroid-stimulating hormone (TSH) level was not correlated with body composition parameters in females. In females, free triiodothyronine (FT3) level was positively correlated with body mass index (BMI), fat-free mass index (FFMI), and skeletal muscle index (SMI), and was negatively correlated with extracellular water fraction (EWF). In males, FT3 level was positively correlated with waist circumference (WC) and SMI and negatively correlated with EWF. Free thyroxine (FT4) level in both women and men was positively correlated with body fat mass (BFM) and left lower-limb muscle mass (LLLMM). Moreover, in males, FT4 level was correlated with more body composition parameters. In euthyroid T2DM patients, FT3 level was positively correlated with SMI and negatively correlated with EWF, while FT4 level was positively correlated with BFM and LLLMM. CONCLUSIONS:Thyroid function can affect body composition in euthyroid T2DM patients. Thyroid function is more likely to affect the fat and muscle distribution of males than females.

Systemic lupus erythematosus (SLE) represents an autoimmune disorder that affects multiple systems. In the treatment of this condition, the focus primarily revolves around inflammation suppression and immunosuppression. Consequently, targeted therapy has emerged as a prevailing approach. Currently, the quest for highly sensitive and specifically effective targets has gained significant momentum in the context of SLE treatment. Lymphocyte activation gene-3 (LAG-3) stands out as a crucial inhibitory receptor that binds to pMHC-II, thereby effectively dampening autoimmune responses. Fibrinogen-like protein 1 (FGL1) serves as the principal immunosuppressive ligand for LAG-3, and their combined action demonstrates a potent immunosuppressive effect. This intricate mechanism paves the way for potential SLE treatment by targeting LAG-3 with FGL1. This work provides a comprehensive summary of LAG-3's role in the pathogenesis of SLE and elucidates the feasibility of leveraging FGL1 as a therapeutic approach for SLE management. It introduces a novel therapeutic target and opens up new avenues of therapeutic consideration in the clinical context of SLE treatment.

Objectives: To appraise the causal effect of systemic lupus erythematosus (SLE) for risk of Coronary heart disease (CHD). Methods: We selected single nucleotide polymorphisms (SNPs) associated with SLE as instrumental variables (IVs) from three independent genome-wide association studies (GWAS), the three largest to date for SLE of European ancestry. Then we conducted two-sample Mendelian randomization (2SMR) analyses to estimate the effects of IVs on the odds of CHD and traditional coronary risk factors (including high LDL cholesterol levels, low HDL cholesterol levels, Apolipoprotein A-I, Apolipoprotein B, diabetes mellitus, and hypertension). Additionally, we searched for common risk loci between SLE and premature coronary atherosclerosis. Furthermore, we retrospectively reviewed the lipid profile of treatment-naïve SLE patients and age-matched healthy controls. Results: Genetically predicted SLE did not increase the odds of CHD. Nevertheless, we found mild causal relationships between SLE and decreased HDL cholesterol levels, and between SLE and decreased apolipoprotein A-I. There was one common risk locus (rs597808) between SLE and premature coronary atherosclerosis at a genome-wide significance level ( P <5 × 10 ⁻⁸ ). Retrospective analysis showed decreased HDL-cholesterol (0.98±0.516mmol/L vs. 1.46±0.307mmol/L in female, 0.76±0.199mmol/L vs. 1.19±0.257mmol/L in male; both P <0.001) and apolipoprotein A-I (1.06±0.314g/L vs. 1.37±0.205g/L in female, 0.87±0.174g/L vs. 1.24±0.200g/L in male; both P <0.001) in naïve SLE patients. Conclusion: SLE may accelerate coronary atherosclerosis in young patients by reducing HDL cholesterol and apolipoprotein A-I intrinsically, but it seems not to play a predominant role in CHD development in old patients.