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1.
Front Immunol ; 12: 762006, 2021.
Article in English | MEDLINE | ID: covidwho-1477832

ABSTRACT

As the coronavirus disease 2019 (COVID-19) pandemic is ongoing and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging, there is an urgent need for COVID-19 vaccines to control disease outbreaks by herd immunity. Surveillance of rare safety issues related to these vaccines is progressing, since more granular data emerge with regard to adverse events of COVID-19 vaccines during post-marketing surveillance. Interestingly, four cases of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) presenting with pauci-immune crescentic glomerulonephritis (GN) after COVID-19 mRNA vaccination have already been reported. We here expand our current knowledge of this rare but important association and report a case of AAV presenting with massive rhabdomyolysis and pauci-immune crescentic GN after Pfizer-BioNTech COVID-19 mRNA vaccination. As huge vaccination programs are ongoing worldwide, post-marketing surveillance systems must continue to assess vaccine safety important for the detection of any events associated with COVID-19 vaccination. This is especially relevant in complex diseases where diagnosis is often challenging, as in our patient with AAV presenting with massive rhabdomyolysis and pauci-immune crescentic GN.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , COVID-19 Vaccines/adverse effects , Glomerulonephritis/pathology , Rhabdomyolysis/pathology , Aged , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology , Antibodies, Antineutrophil Cytoplasmic/blood , Antibodies, Antineutrophil Cytoplasmic/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Female , Glomerulonephritis/diagnosis , Glomerulonephritis/immunology , Humans , RNA, Messenger/immunology , Rhabdomyolysis/diagnosis , Rhabdomyolysis/immunology
2.
Cells ; 10(7)2021 07 04.
Article in English | MEDLINE | ID: covidwho-1394870

ABSTRACT

Neutrophil extracellular traps (NETs) are web-like structures of decondensed extracellular chromatin fibers and neutrophil granule proteins released by neutrophils. NETs participate in host immune defense by entrapping pathogens. They are pro-inflammatory in function, and they act as an initiator of vascular coagulopathies by providing a platform for the attachment of various coagulatory proteins. NETs are diverse in their ability to alter physiological and pathological processes including infection and inflammation. In this review, we will summarize recent findings on the role of NETs in bacterial/viral infections associated with vascular inflammation, thrombosis, atherosclerosis and autoimmune disorders. Understanding the complex role of NETs in bridging infection and chronic inflammation as well as discussing important questions related to their contribution to pathologies outlined above may pave the way for future research on therapeutic targeting of NETs applicable to specific infections and inflammatory disorders.


Subject(s)
Cardiovascular System/pathology , Extracellular Traps/metabolism , Infections/pathology , Inflammation/pathology , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , Humans , Infections/virology , Models, Biological
3.
Front Immunol ; 11: 599417, 2020.
Article in English | MEDLINE | ID: covidwho-1000095

ABSTRACT

The complement system comprises the frontline of the innate immune system. Triggered by pathogenic surface patterns in different pathways, the cascade concludes with the formation of a membrane attack complex (MAC; complement components C5b to C9) and C5a, a potent anaphylatoxin that elicits various inflammatory signals through binding to C5a receptor 1 (C5aR1). Despite its important role in pathogen elimination, priming and recruitment of myeloid cells from the immune system, as well as crosstalk with other physiological systems, inadvertent activation of the complement system can result in self-attack and overreaction in autoinflammatory diseases. Consequently, it constitutes an interesting target for specialized therapies. The paradigm of safe and efficacious terminal complement pathway inhibition has been demonstrated by the approval of eculizumab in paroxysmal nocturnal hematuria. In addition, complement contribution in rare kidney diseases, such as lupus nephritis, IgA nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, or antineutrophil cytoplasmic antibody-associated vasculitis has been demonstrated. This review summarizes the involvement of the terminal effector agents of the complement system in these diseases and provides an overview of inhibitors for complement components C5, C5a, C5aR1, and MAC that are currently in clinical development. Furthermore, a link between increased complement activity and lung damage in severe COVID-19 patients is discussed and the potential for use of complement inhibitors in COVID-19 is presented.


Subject(s)
Complement C5a/antagonists & inhibitors , Complement Inactivating Agents/therapeutic use , Complement Membrane Attack Complex/antagonists & inhibitors , Kidney Diseases/drug therapy , Receptor, Anaphylatoxin C5a/antagonists & inhibitors , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , Antibodies, Monoclonal, Humanized/therapeutic use , Complement Activation/immunology , Complement System Proteins/metabolism , Glomerulonephritis, IGA/drug therapy , Glomerulonephritis, IGA/pathology , Humans , Kidney/pathology , Kidney Diseases/immunology , Kidney Diseases/pathology , Lupus Nephritis/drug therapy , Lupus Nephritis/pathology
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