Microparticles in Autoimmunity: Cause or Consequence of Disease?

Microparticles (MPs) are small (100 nm - 1 um) extracellular vesicles derived from the plasma membrane of dying or activated cells. MPs are important mediators of intercellular communication, transporting proteins, nucleic acids and lipids from the parent cell to other cells. MPs resemble the state of their parent cells and are easily accessible when released into the blood or urine.

To NET or not to NET:current opinions and state of the science regarding the formation of neutrophil extracellular traps.

Since the discovery and definition of neutrophil extracellular traps (NETs) 14 years ago, numerous characteristics and physiological functions of NETs have been uncovered. Nowadays, the field continues to expand and novel mechanisms that orchestrate formation of NETs, their previously unknown properties, and novel implications in disease continue to emerge. The abundance of available data has also led to some confusion in the NET research community due to contradictory results and divergent scientific concepts, such as pro- and anti-inflammatory roles in pathologic conditions, demarcation from other forms of cell death, or the origin of the DNA that forms the NET scaffold.

Cleaved N-terminal histone tails distinguish between NADPH oxidase (NOX)-dependent and NOX-independent pathways of neutrophil extracellular trap formation.

Objectives: Neutrophil extracellular traps (NETs) act in various rheumatic diseases. Although NET formation was originally described as a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-dependent pathway, it appears that there are also NOX-independent pathways of NET release. Currently, no tools are available that can discriminate between both NET-forming pathways.

Autoantibodies Recognizing Secondary NEcrotic Cells Promote Neutrophilic Phagocytosis and Identify Patients With Systemic Lupus Erythematosus.

Deficient clearance of apoptotic cells reportedly contributes to the etiopathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). Based on this knowledge, we developed a highly specific and sensitive test for the detection of SLE autoantibodies (AAb) utilizing secondary NEcrotic cell (SNEC)-derived material as a substrate. The goal of the present study was to validate the use of SNEC as an appropriate antigen for the diagnosis of SLE in large cohort of patients.

Interleukin-6 is essential for glomerular immunoglobulin A deposition and the development of renal pathology in Cd37-deficient mice.

Immunoglobulin A (IgA) nephropathy (IgAN), the most common glomerulonephritis worldwide, is characterized by IgA depositions in the kidney. Deficiency of CD37, a leukocyte-specific tetraspanin, leads to spontaneous development of renal pathology resembling IgAN. However, the underlying molecular mechanism has not been resolved.

Acetylated Histones in Apoptotic Microparticles Drive the Formation of Neutrophil Extracellular Traps in Active Lupus Nephritis.

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies against nuclear components. Lupus nephritis (LN) is the major cause of morbidity and mortality in patients with SLE. Central to the pathogenesis of SLE is the accumulation of cellular waste, especially apoptotic microparticles (MPs), which stimulates diverse immune reactions including the formation of neutrophil extracellular traps (NETs).

Neutrophil Extracellular Traps Drive Endothelial-to-Mesenchymal Transition.

Objective: An excessive release and impaired degradation of neutrophil extracellular traps (NETs) leads to the continuous exposure of NETs to the endothelium in a variety of hematologic and autoimmune disorders, including lupus nephritis. This study aims to unravel the mechanisms through which NETs jeopardize vascular integrity.

Approach And Results: Microvascular and macrovascular endothelial cells were exposed to NETs, and subsequent effects on endothelial integrity and function were determined in vitro and in vivo.

Blood-borne phagocytes internalize urate microaggregates and prevent intravascular NETosis by urate crystals.

Hyperuricemia is strongly linked to cardiovascular complications including atherosclerosis and thrombosis. In individuals with hyperuricemia, needle-shaped monosodium urate crystals (nsMSU) frequently form within joints or urine, giving rise to gouty arthritis or renal calculi, respectively. These nsMSU are potent instigators of neutrophil extracellular trap (NET) formation.

Circulating Apoptotic Microparticles in Systemic Lupus Erythematosus Patients Drive the Activation of Dendritic Cell Subsets and Prime Neutrophils for NETosis.

Objective: Circulating chromatin-containing apoptotic material and/or neutrophil extracellular traps (NETs) have been proposed to be an important driving force for the antichromatin autoimmune response in patients with systemic lupus erythematosus (SLE). The aim of this study was to determine the exact nature of microparticles in the circulation of SLE patients and to assess the effects of the microparticles on the immune system.

Methods: We analyzed microparticles isolated from the plasma of patients with SLE, rheumatoid arthritis (RA), and systemic sclerosis (SSc), as well as from healthy subjects.

Breaking immunological tolerance in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a fairly heterogeneous autoimmune disease of unknown etiology that mainly affects women in the childbearing age. SLE is a prototype type III hypersensitivity reaction in which immune complex depositions cause inflammation and tissue damage in multiple organs. Two distinct cell death pathways, apoptosis and NETosis, gained a great deal of interest among scientists, since both processes seem to be deregulated in SLE.

Apoptosis and NET formation in the pathogenesis of SLE.

Systemic Lupus Erythematosus is an autoimmune disease characterized by the formation of anti-nuclear autoantibodies, particularly anti-chromatin. Although the aetiology of the disease has not yet been fully elucidated, several mechanisms have been proposed to be involved. Due to an aberrant apoptosis or decreased removal of apoptotic cells, apoptotic blebs containing chromatin are released.