Biallelic mutations of three prime repair exonuclease 1 (TREX1) cause the lupus-like disease Aicardi-Goutières syndrome in which accumulation of a yet unknown endogenous DNA substrate of TREX1 triggers a cyclic GMP-AMP synthase-dependent type I IFN response and systemic autoimmunity. Products of reverse transcription originating from endogenous retroelements have been suggested to be a major substrate for TREX1, and reverse transcriptase inhibitors (RTIs) were proposed as a therapeutic option in autoimmunity ensuing from defects of TREX1. In this study, we treated mice with RTIs. The serum RTI levels reached were sufficient to block retrotransposition of endogenous retroelements. However, the treatment did not reduce the spontaneous type I IFN response and did not ameliorate lethal inflammation. Furthermore, long interspersed nuclear elements 1 retrotransposition was not enhanced in the absence of Trex1. Our data do not support the concept of retroelement-derived cDNA as key triggers of systemic autoimmunity in Trex1-deficient humans and mice and motivate the continuing search for the pathogenic IFN-inducing Trex1 substrate.

Background and aims Thromboelastometry (TEM) is superior to standard coagulation tests in the management of bleedings / invasive procedures in patients with liver cirrhosis. In contrast, the role of TEM as a prognostic parameter in liver cirrhosis is not well established. We therefore aimed to assess the role of TEM in predicting survival of outpatients with liver cirrhosis. Methods TEM was performed in consecutive outpatients with liver cirrhosis admitted in 2018 and 2019 to the University Hospital Essen. Associations with transplant-free survival were assessed in regression models. Results A number of 145 outpatients with liver cirrhosis were included, of whom 27 received a liver transplant (N = 7) or died (N = 20) within 6 months of follow-up. None of the TEM values was associated with transplant-free survival in this cohort. However, as expected, the classical coagulation tests INR (OR = 8.69 (95% CI 1.63-46.48), P = 0.01), PTT (OR = 1.15 (95% CI 1.04-1.27), P<0.01), as well as antithrombin (OR = 0.96 (95% CI 0.94-0.99), P<0.01), and protein C (OR = 0.96 (95% CI 0.92-0.99), P<0.01) were significantly associated with transplant-free survival. Conclusion In contrast to the superiority of TEM over classical coagulation tests to guide transfusion of blood products in patients with liver cirrhosis, TEM has no relevance in predicting mortality in outpatients with liver cirrhosis.

Objective To assess whether a healthy lifestyle is associated to beneficial effects on various systemic lupus erythematosus (SLE) health domains. Methods In a cross-sectional study, Mediterranean Diet Adherence Score (MEDAS), physical activity energy expenditure (PAEE), and smoking status were assessed by questionnaires, along with clinical parameters and various health domains including Systemic Lupus Disease Activity Score (SLEDAI), Depression Scale (CES-D), Fatigue Severity (FSS), functional status (FFbH), physical and mental quality of life (PCS, MCS). Lifestyle choices were assessed with respect to health domains by linear regression modeling. Additionally, SLE patients with a healthy lifestyle (MEDAS ≥ 4, ≥ 1 h sport per week, no smoking) were compared to those without by Wilcoxon’s signed-rank test. Results 49 of 145 SLE patients (44.3 ± 31.7 years, 87.6% female) followed a healthy lifestyle and showed a higher physical quality of life (β = 4.5 (95%-CI 1.5–7.9) p = 0.01), lower depression (β = −5.0 (−8.2 to −0.2) p = 0.02) and lower fatigue (β = −0.8 (−1.5 to −0.2) p = 0.01) independently of SLE disease activity. Furthermore, dsDNA-antibodies were lower (146 ± 540 vs 266 ± 146 U/mL, p = 0.049). In a more detailed analysis, physical activity had the highest impact on the various health domains when compared to smoking or diet adherence, which was consistent even after adjusting for multiple potential confounders. Each 1,000 kcal of weekly PAEE was associated to a 1.8 (0.9–2.6) point increase in the PCS ( p = 0.0001), a 0.2 (0.03–0.4) point decrease in the CES-D ( p = 0.01) and a 2.8 (1.2–4.4) point increase in the FFbH ( p = 0.0006). Conclusion A healthy lifestyle, especially physical activity is associated with beneficial effects including quality of life, depression and fatigue in SLE.

No abstract

No abstract