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Complement Pathway Dynamics and Kidney Immune Response in C3 Glomerulopathy

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The following is a summary of “Complement Terminal Pathway Activation and Intrarenal Immune Response in C3 Glomerulopathy,” published in the May 2024 issue of Nephrology by Meuleman et al.


Overactivation of complement alternative pathways often leads to C3 glomerulopathy. Although some parts of this response have been well-studied, their occurrence and consequences are still being determined.

Researchers conducted a retrospective study exploring how activating specific immune pathways impacts C3 glomerulopathy and its progression. 

They analyzed 42 patients diagnosed with C3 glomerulopathy, reviewing histological parameters centrally. Terminal pathway activation was checked using Kidney C5b-9 staining, and transcriptomic analysis was performed to understand the immune response within the kidneys. 

The results showed that in most biopsies (88%), C5b-9 deposits were found in glomeruli. C5b-9 levels categorized these biopsies: 15 low (36%), 15 intermediate (36%), and 12 high (28%). Patients with high C5b-9 had significantly higher histological chronicity scores (P=0.005) and lower outcome-free survival (P=0.001). After adjustment, high glomerular C5b-9 remained linked to poor kidney prognosis. About one-third of immune genes studied were upregulated in C3 glomerulopathy compared to controls. Unsupervised gene clustering identified a subgroup with high glomerular C5b-9, immune activation, fibrosis, and increased chronicity scores. 

Investigators concluded that in patients with C3 glomerulopathy, kidney terminal pathway activation links to distinct tissue features and disease outlook. 

Source: journals.lww.com/jasn/abstract/9900/complement_terminal_pathway_activation_and.310.aspx

 

The post Complement Pathway Dynamics and Kidney Immune Response in C3 Glomerulopathy first appeared on Physician's Weekly.


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