Sex-specific differences in SLE - Significance in the experimental setting of inflammation and kidney damage in MRL-Faslpr mice.

Animal models are an important tool in the research of chronic autoimmune diseases, like systemic lupus erythematosus (SLE). MRL-Faslpr mice are one of different lupus models that develop spontaneously an SLE-like disease with autoantibodies and immune complex deposition that leads into damage of different organs. In contrast to human SLE, both sexes of MRL-Faslpr mice develop a similar autoimmune disease. Due to the sex bias in human and the delayed disease progression in male MRL-Faslpr mice, the majority of studies have been performed in female mice. To determine the suitability of male MRL-Faslpr mice for SLE research, especially with regard to the 3 R-principle and animal welfare, analyses of phenotype, inflammation and damage with focus on kidney and spleen were performed in mice of both sexes. Female mice developed lymphadenopathy and skin lesions earlier as males. At an age of 3.5 month, more immune cells infiltrated kidney and spleen in females compared to males. At the age of 5 months, however, substantially less sex-specific differences were detected. Since other studies have shown differences between both sexes on other manifestations like autoimmune pancreatitis and Sjögren syndrome in MRL-Faslpr mice, the use of male mice as part of 3 R-principle and animal welfare must be carefully considered.

A20 in Kidney Transplantation and Autoimmunity.

A20, the central inhibitor of NFκB, has multiple anti-inflammatory properties, making it an interesting target in kidney autoimmune disease and transplant biology. It has been shown to be able to inhibit inflammatory functions in macrophages, dendritic cells, T cells, and B cells in various ways, leading to less tissue damage and better graft outcomes. In this review, we will discuss the current literature regarding A20 in kidney transplantation and autoimmunity. Future investigations on animal models and in existing immunosuppressive therapies are needed to establish A20 as a therapeutic target in kidney transplantation and autoimmunity. Cell-based therapies, modified viruses or RNA-based therapies could provide a way for A20 to be utilized as a promising mediator of inflammation and tissue damage.

Validation of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in an academic tertiary care centre.

OBJECTIVES: To assess the sensitivity and specificity of the 2019 EULAR/American College of Rheumatology (ACR) classification criteria for systemic lupus erythematosus (SLE) in outpatients at an academic tertiary care centre and to compare them to the 1997 ACR and the 2012 Systemic Lupus International Collaborating Clinics criteria. METHODS: Prospective and retrospective observational cohort study. RESULTS: 3377 patients were included: 606 with SLE, 1015 with non-SLE autoimmune-mediated rheumatic diseases (ARD) and 1756 with non-ARD diseases (hepatocellular carcinoma, primary biliary cirrhosis, autoimmune hepatitis). The 2019 criteria were more sensitive than the 1997 criteria (87.0% vs 81.8%), but less specific (98.1% vs 99.5% in the entire cohort and 96.5% vs 98.8% in patients with non-SLE ARD), resulting in Youden Indexes for patients with SLE/non-SLE ARD of 0.835 and 0.806, respectively. The most sensitive items were history of antinuclear antibody (ANA) positivity and detection of anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies. These were also the least specific items. The most specific items were class III/IV lupus nephritis and the combination of low C3 and low C4 complement levels, followed by class II/V lupus nephritis, either low C3 or low C4 complement levels, delirium and psychosis, when these were not attributable to non-SLE causes. CONCLUSIONS: In this cohort from an independent academic medical centre, the sensitivity and specificity of the 2019 lupus classification criteria were confirmed. Overall agreement of the 1997 and the 2019 criteria was very good.