Search

Neutrophil extracellular traps (NETs) are fibrous networks which protrude from the membranes of activated neutrophils. NETs are found in a variety of conditions such as infection, malignancy, atherosclerosis, and autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), psoriasis, and gout. Studies suggest that an imbalance between “NETosis,” which is a process by which NETs are formed, and NET degradation may be associated with autoimmune diseases. Neutrophils, interleukin-8, ANCA and other inflammatory molecules are considered to play a key role in NET formation. Prolonged exposure to NETs-related cascades is associated with autoimmunity and increases the chance of systemic organ damage. In this review, we discuss the roles of various inflammatory molecules in relation to NETs. We also describe the role of NETs in the pathogenesis of autoimmune diseases and discuss the possibility of using targeted therapies directed to NETs and associated molecules to treat autoimmune diseases. [ABSTRACT FROM AUTHOR]

Extracorporeal treatments have been used since the 1970s in the management of systemic lupus erythematosus (SLE). A randomised controlled trial comparing the efficacy of standard of care (SOC) combined with plasma exchange against SOC alone in patients with lupus nephritis revealed no difference in terms of renal outcome. Subsequently, initial expectations have been dampened and further experience with plasma exchange is mainly limited to observational studies and single case reports. Beneficial effects have been reported in patients with refractory disease course or in pregnancy with prior complications due to SLE and antiphospholipid syndrome. A more specific form of extracorporeal treatment, immunoadsorption (IAS), has emerged as a valuable option in the treatment of SLE. In line with the plasma exchange experience, IAS seems to have beneficial effects in patients with refractory disease, contraindications to standard immunosuppression or during pregnancy. The mechanism IAS relates to autoantibody removal but for plasma exchange removal of activated complement components, coagulation factors, cytokines and microparticles may also be relevant. Both treatment forms have good safety profiles although reactions to blood product replacement in plasma exchange and procedure related complications such as bleeding or catheter-related infections have occurred. There is a need to more clearly define the clinical utility of plasma exchange and IAS in refractory lupus and APS subgroups. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus is a chronic autoimmune disease characterized by loss of tolerance against nuclear and cytoplasmic self-antigens, induction of immunity and tissue inflammation. Lupus nephritis (LN), the most important predictor of morbidity in SLE, develops in almost 30% of SLE patients at disease onset and in up to 50-60% within the first 10 years. Firstly, in this review, we put the pathogenic mechanisms of the disease into a conceptual frame, giving emphasis to the role of the innate immune system in this loss of self-tolerance and the induction of the adaptive immune response. In this aspect, many mechanisms have been described such as dysregulation and acceleration of cell-death pathways, an aberrant clearance and overload of immunogenic acid-nucleic-containing debris and IC, and the involvement of antigen-presenting cells and other innate immune cells in the induction of this adaptive immune response. This result in a clonal expansion of autoreactive lymphocytes with generation of effector T-cells, memory B-cells and plasma cells that produce autoantibodies that will cause kidney damage. Secondly, we review the immunological pathways of damage in the kidney parenchyma, initiated by autoantibody binding and immune complex deposition, and followed by complement-mediated microvascular injury, activation of kidney stromal cells and the recruitment of leukocytes. Finally, we summarize the rationale for the treatment of LN, from conventional to new targeted therapies, focusing on their systemic immunologic effects and the minimization of podocytary damage. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a multi-systemic severe autoimmune disease which results from the irreversible loss of self-tolerance and impaired molecular responses, especially an altered interferon signature. We synthesized all meta-analyses reporting a genetic association of SLE, and further investigated their validity to discover false positive results under Bayesian methods. We executed a PubMed search to extract the respective results regarding gene polymorphisms of SLE, published until June 30th 2017 and selected a single result per genetic variant among duplicates. Among 133 significant genotype comparisons, 45 (34%) were found noteworthy under both false positive report probability (FPRP) and Bayesian false discovery probability (BFDP). From the meta-analysis of genome-wide association studies (GWAS), we could confirm that all significant comparisons were noteworthy under both Bayesian approaches. Both approaches may be advantageous for determining whether the reported associations are genuine, especially for interpreting results from observational studies instead of GWAS whose significance was determined in a more strict manner. When determining results from GWAS with a p -value ranging between 0.05 and 5 × 10 −8 , other statistical approaches, rather than single standard significance may be beneficial. Taking into account these considerations, a proportion of meta-analyses claimed statistical significance, but these results need to be interpreted with caution. [ABSTRACT FROM AUTHOR]