Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and patients are under an increased risk for cardiovascular (CV) events and mortality. The increased CV risk for patients with SLE seems to be caused by a premature and accelerated atherosclerosis, attributable to lupus-specific risk factors (i.e., increased systemic inflammation, altered immune status), apart from traditional CV risk factors. To date, there is no established experimental model to explore the pathogenesis of this increased CV risk in SLE patients. Methods: Here we investigated whether MRL-Fas^lpr mice, which develop an SLE-like phenotype, may serve as a model to study lupus-mediated vascular disease. Therefore, MRL-Fas^lpr, MRL-++, and previously generated Il6^−/− MRL-Fas^lpr mice were used to evaluate vascular changes and possible mechanisms of vascular dysfunction and damage. Results: Contrary to MRL-++ control mice, lupus-prone MRL-Faslpr mice exhibited a pronounced vascular and perivascular leukocytic infiltration in various organs; expression of pro-inflammatory cytokines in the aorta and kidney was augmented; and intima-media thickness of the aorta was increased. IL-6 deficiency reversed these changes and restored aortic relaxation. Conclusion: Our findings demonstrate that the MRL-Fas^lpr mouse model is an excellent tool to investigate vascular damage in SLE mice. Moreover, IL-6 promotes vascular inflammation and damage and could potentially be a therapeutic target for the treatment of accelerated arteriosclerosis in SLE.

Hemodialysis patients (HDP) and kidney transplant recipients (KTR) have a high risk of infection with SARS-CoV-2 with poor clinical outcomes. Because of this, vaccination of these groups of patients against SARS-CoV-2 is particularly important. However, immune responses may be impaired in immunosuppressed and chronically ill patients. Here, our aim was to compare the efficacy of an mRNA-based vaccine in HDP, KTR, and healthy subjects. Design: In this prospective observational cohort study, the humoral and cellular response of prevalent 192 HDP, 50 KTR, and 28 healthy controls (HC) was assessed 1, 2, and 6 months after the first immunization with the BNT162b2 mRNA vaccine. Results: After 6 months, 97.5% of HDP, 37.9% of KTR, and 100% of HC had an antibody response. Median antibody levels were 1539.7 (±3355.8), 178.5 (±369.5), and 2657.8 (±2965.8) AU/mL in HDP, KTR, and HC, respectively (p ≤ 0.05). A SARS-CoV-2 antigen-specific cell response to vaccination was found in 68.8% of HDP, 64.5% of KTR, and 90% of HC. Conclusion: The humoral response rates to mRNA-based vaccination of HDPs are comparable to HCs, but antibody titers are lower. Furthermore, HDPs have weaker T-cell response to vaccination than HCs. KTRs have very low humoral and antigen-specific cellular response rates and antibody titers, which requires other vaccination strategies in addition to booster vaccination.

Dear Editor, in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, patients with autoimmune-mediated rheumatic diseases (ARD) may have an increased risk to develop severe illness. Their malfunctioning immune system as well as the medical immunosuppression render them more susceptible for stronger and longer disease. In addition, vaccination may not be as efficacious as in the general population, which further adds to their risk of severe coronavirus 2019 disease (COVID-19).

Post-Covid syndrome is a debilitating condition which may be caused and/or aggravated by autoantibodies. The current study aimed to determine whether autoantibody depletion by immunoadsorption is effective to reduce the symptom burden of patients with post-Covid syndrome. IAMPOCO was a randomised, patient-blinded, sham-controlled crossover trial of immunoadsorption with tryptophan adsorbers versus sham treatment in patients with post-Covid syndrome at a tertiary academic care centre. The primary outcome was the difference in change in symptom severity before and after the respective therapies. Secondary outcomes included treatment safety, prevalence of autoantibodies against G protein-coupled receptors (adrenergic and muscarinergic receptors), and the influence of treatment on autoantibody levels. 40 patients with post-Covid syndrome and a symptom severity of at least 2 on the Post-Covid-19 Functional Scale were included and randomised to a treatment sequence. There was no difference in change in symptom severity between immunoadsorption and sham; odds ratio in Post-Covid-19 Functional Scale, OR = 1.17 (95% CI, 0.41–3.36; p = 0.771), mean difference in MFI-20 2.4 (95% CI, −3.7–8.5; p = 0.437), in CFS 0.09 (95% CI, −4.5 to 4.7; p = 0.970), in Bell-Scale −2.6 (95% CI, −6.9 to 1.8; p = 0.246), in MoCA score −0.01 (95% CI, −1.2 to 1.1, p = 0.993) and in Handgrip-strength deviation from individual normal value 1.3 (−0.83 to 3.5, p = 0.234). 34 adverse events occurred, 10 during or after sham treatment and 24 during or after immunoadsorption. Autoantibodies against G protein-coupled receptors were depleted by immunoadsorption but not sham treatment. Immunoadsorption was not effective in reducing symptom burden in post-Covid syndrome. Ministry of Health, state of Rhineland-Palatinate; Mainz University Medical Centre; DIAMED Medical Technology. Trial Registration: ClinicalTrials.gov, number NCT05841498.

Background/Objectives: Pre-analytical variation is a major challenge in metabolomics, yet most stability studies have focused on healthy volunteers and have overlooked the impact of disease and medication. To address this gap, we conducted a pilot study in systemic lupus erythematosus (SLE) to assess serum metabolite stability under delayed centrifugation. Methods: Peripheral blood from 10 SLE patients and 5 healthy controls (HC) was stored at room temperature for 1–24 h before processing and analyzed by untargeted LC-MS-based metabolomics. This design enabled direct evaluation of the effect of pre-analytical delay within the context of clinical heterogeneity. Results: Principal component trajectories showed reproducible temporal shifts in HC but dispersed patterns in SLE, indicating disease- and treatment-related influences. Linear mixed-effects models identified metabolites with condition-specific kinetics, including glucose, choline, glycerophosphocholine, and pyroglutamic acid. Mycophenolate intake was further associated with distinct AMP dynamics. Conclusions: These findings demonstrate that both disease state and medication reshape apparent metabolite stability, highlighting the need for strictly controlled sample handling and well-characterized clinical cohorts in metabolomics studies.

Objectives: To investigate the therapeutic potential of caspase-1 inhibition in systemic lupus erythematosus (SLE) and lupus nephritis (LN) using the MRL- Fas ^lpr mouse model. Methods: Female Murphy Roths large (MRL)- Fas ^lpr mice were treated with a caspase-1 inhibitor (pralnacase) or sham treatment from 2.5 to 5.5 months of age. Disease progression was assessed through analysis of systemic and renal parameters, including proteinuria, blood urea nitrogen, kidney histopathology and immune cell infiltration. Cytokine expression and caspase activity were measured to elucidate the mechanism of action. Additional experiments with interleukin (IL)-1 receptor antagonist and pancaspase inhibition treatment as well as post-disease onset intervention were conducted. Results: Caspase-1 inhibition significantly reduced systemic inflammation, lymphadenopathy and skin lesions in MRL- Fas ^lpr mice. Treated mice exhibited decreased proteinuria, improved renal function and reduced kidney pathology. The treatment specifically targeted caspase-1 activity, leading to decreased IL-18 levels as well as attenuated immune cell activation and infiltration in the kidneys. Selective caspase-1 inhibition showed comparable results with pancaspase inhibition. IL-1 receptor antagonist treatment did not significantly affect disease progression, suggesting IL-18 as the primary driver of pathology. Post-disease onset intervention with caspase-1 inhibition also showed efficacy, although to a lesser extent than pre-onset treatment. Conclusions: Caspase-1 inhibition effectively ameliorates both systemic and renal manifestations of SLE in MRL- Fas ^lpr mice, primarily through suppression of IL-18-mediated inflammation. This study identifies caspase-1 as a promising therapeutic target for SLE and LN, warranting further investigation in clinical trials.