Morphofunctional Effects of C5 Convertase Blockade in Immune Complex-Mediated Membranoproliferative Glomerulonephritis: Report of Two Cases with Evidence of Terminal Complement Activation

Nephron ◽  
2020 ◽  
Vol 144 (4) ◽  
pp. 195-203
Author(s):  
Camillo Carrara ◽  
Manuel Alfredo Podestà ◽  
Mauro Abbate ◽  
Paola Rizzo ◽  
Rossella Piras ◽  
...  
Keyword(s):  
Immune Complex ◽  
Complement Activation ◽  
Membranoproliferative Glomerulonephritis ◽  
Terminal Complement

scholarly journals Topical Application of Mesenchymal Stem Cell Exosomes Alleviates the Imiquimod Induced Psoriasis-Like Inflammation

2021 ◽  
Vol 22 (2) ◽  
pp. 720
Author(s):  
Bin Zhang ◽  
Ruenn Chai Lai ◽  
Wei Kian Sim ◽  
Andre Boon Hwa Choo ◽  
Ellen Birgit Lane ◽  
...  
Keyword(s):  
Stratum Corneum ◽  
Complement Activation ◽  
Alternative Therapy ◽  
Mouse Skin ◽  
Extracellular Traps ◽  
Cellular Source ◽  
Skin Explants ◽  
Therapy Strategies ◽  
Terminal Complement

Severe psoriasis, a chronic inflammatory skin disease is increasingly being effectively managed by targeted immunotherapy but long-term immunotherapy poses health risk and loss of response. Therefore, there is a need for alternative therapy strategies. Mesenchymal stem/stromal cell (MSC) exosomes are widely known for their potent immunomodulatory properties. Here we investigated if topically applied MSC exosomes could alleviate psoriasis-associated inflammation. Topically applied fluorescent exosomes on human skin explants were confined primarily to the stratum corneum with <1% input fluorescence exiting the explant over a 24-h period. Nevertheless, topically applied MSC exosomes in a mouse model of imiquimod (IMQ) psoriasis significantly reduced IL-17 and terminal complement activation complex C5b-9 in the mouse skin. MSC exosomes were previously shown to inhibit complement activation, specifically C5b-9 complex formation through CD59. Infiltration of neutrophils into the stratum corneum is characteristic of psoriasis and neutrophils are a major cellular source of IL-17 in psoriasis through the release of neutrophil extracellular traps (NETs). We propose that topically applied MSC exosomes inhibit complement activation in the stratum corneum and this alleviates IL-17 release by NETS from neutrophils that accumulate in and beneath the stratum corneum.

Effects of Immune Complex Formation and Complement Activation on Circulating Platelets in the Primate

1999 ◽  
Vol 91 (1) ◽  
pp. 99-105 ◽  
Author(s):  
Daniel J. Birmingham ◽  
Lee A. Hebert ◽  
Xiao-Ping Shen ◽  
Paul Higgins ◽  
C.Grace Yeh ◽  
...  
Keyword(s):  
Complex Formation ◽  
Immune Complex ◽  
Complement Activation ◽  
Immune Complex Formation

Complement C5 inhibition protects against hemolytic anemia and acute kidney injury in anthrax peptidoglycan-induced sepsis in baboons

2021 ◽  
Vol 118 (37) ◽  
pp. e2104347118
Author(s):  
Ravi Shankar Keshari ◽  
Narcis Ioan Popescu ◽  
Robert Silasi ◽  
Girija Regmi ◽  
Cristina Lupu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Hemolytic Anemia ◽  
Complement Activation ◽  
Inflammatory Responses ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Kidney Injury ◽  
Multiple Organ ◽  
Immune Recognition ◽  
Gram Positive ◽  
Terminal Complement

Late-stage anthrax infections are characterized by dysregulated immune responses and hematogenous spread of Bacillus anthracis, leading to extreme bacteremia, sepsis, multiple organ failure, and, ultimately, death. Despite the bacterium being nonhemolytic, some fulminant anthrax patients develop a secondary atypical hemolytic uremic syndrome (aHUS) through unknown mechanisms. We recapitulated the pathology in baboons challenged with cell wall peptidoglycan (PGN), a polymeric, pathogen-associated molecular pattern responsible for the hemostatic dysregulation in anthrax sepsis. Similar to aHUS anthrax patients, PGN induces an initial hematocrit elevation followed by progressive hemolytic anemia and associated renal failure. Etiologically, PGN induces erythrolysis through direct excessive activation of all three complement pathways. Blunting terminal complement activation with a C5 neutralizing peptide prevented the progressive deposition of membrane attack complexes on red blood cells (RBC) and subsequent intravascular hemolysis, heme cytotoxicity, and acute kidney injury. Importantly, C5 neutralization did not prevent immune recognition of PGN and shifted the systemic inflammatory responses, consistent with improved survival in sepsis. Whereas PGN-induced hemostatic dysregulation was unchanged, C5 inhibition augmented fibrinolysis and improved the thromboischemic resolution. Overall, our study identifies PGN-driven complement activation as the pathologic mechanism underlying hemolytic anemia in anthrax and likely other gram-positive infections in which PGN is abundantly represented. Neutralization of terminal complement reactions reduces the hemolytic uremic pathology induced by PGN and could alleviate heme cytotoxicity and its associated kidney failure in gram-positive infections.

scholarly journals Complement activation pathways in murine immune complex-induced arthritis and in C3a and C5a generationin vitro

2010 ◽  
Vol 159 (1) ◽  
pp. 100-108 ◽  
Author(s):  
N. K. Banda ◽  
B. Levitt ◽  
A. K. Wood ◽  
K. Takahashi ◽  
G. L. Stahl ◽  
...  
Keyword(s):  
Immune Complex ◽  
Complement Activation ◽  
Activation Pathways

Detection of complement activation in immune complex diseases: six methods compared.

1986 ◽  
Vol 32 (12) ◽  
pp. 2170-2174 ◽  
Author(s):  
T Sun ◽  
J Stagias
Keyword(s):  
Immune Complex ◽  
Lupus Erythematosus ◽  
Complement Activation ◽  
Complex Diseases ◽  
Renal Diseases ◽  
Good Resolution ◽  
Gram Negative Bacteremia ◽  
Quantitative Results ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

Abstract We compared the performance of six complement tests: electrophoresis, immunofixation, immunoelectrophoresis, and nephelometric quantifications of C3, C4, and C3d. We used 123 blood samples from 60 control subjects and 63 patients with immune complex diseases: systemic lupus erythematosus, idiopathic thrombocytopenic purpura, rheumatoid arthritis, acquired immunodeficiency syndrome, renal diseases, vasculitis, cryoglobulinemia, Gram-negative bacteremia, Hashimoto's thyroiditis, rheumatic heart disease, malaria, and chronic active hepatitis. Immunofixation and quantification of C3d were better for detecting complement activation, their sensitivity rates (90.5% and 89.3%, respectively) being higher than those of the other tests studied. Immunofixation is a relatively simple and inexpensive test, provides good resolution of protein bands, and yields results that are easily quantified with a densitometer. Nephelometry of C3d provides more rapid and accurate quantitative results than immunofixation, but commercial reagents are not yet available. The causes of false-positive results in complement tests and the mechanisms of complement activation in AIDS are also discussed.

Therapy and outcomes of C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis

2020 ◽  
Author(s):  
Priyanka Khandelwal ◽  
Swati Bhardwaj ◽  
Geetika Singh ◽  
Aditi Sinha ◽  
Pankaj Hari ◽  
...  
Keyword(s):  
Immune Complex ◽  
Membranoproliferative Glomerulonephritis ◽  
C3 Glomerulopathy

scholarly journals Terminal complement activation is increased and associated with disease severity in CIDP

2016 ◽  
Vol 3 (9) ◽  
pp. 730-735 ◽  
Author(s):  
Isaak Quast ◽  
Christian W. Keller ◽  
Falk Hiepe ◽  
Björn Tackenberg ◽  
Jan D. Lünemann
Keyword(s):  
Disease Severity ◽  
Complement Activation ◽  
Terminal Complement
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