Complement system and kidney disease: protective or destructive? - UBC and BCR PWR 02.16.2024

Dr. Pouneh Dokouhaki presents her talk, “Complement system and kidneys - Mission protection or destruction?” as part of BC Renal’s province-wide rounds.
0:04:00 - Introduction
She starts by talking about the history of the discovery of the complement system by Jules Bordet. The complement system is an ancient innate immune mechanism. Overactivation can result in tissue damage, autoimmunity and chronic inflammation, while underactivation results in increased risk of infection.
0:08:00 - Innate immunity against pathogens - specific mechanisms
Dr. Dokouhaki provides an overview of some specific complement pathways, including for permanent low-grade activity, the lectin pathway, and the classical pathway (ie., immune complexes and apoptotic cells).
0:15:00 - Additional roles of the complement system
Dr. Dokouhaki also discusses the role of the complement system in anti-tumor immunity, coagulation, physiology and homeostasis, solubilizing immune complexes, central nervous system development and neurogeneration, and immune regulation. She talks in more detail about B cell activation mechanisms and its relation to kidney disease.
0:30:00 - Laboratory tests for complement system
Dr. Dokouhaki notes there aren’t many good tests for complement system, but it is possible to check for some types of fragments in plasma or other body fluids. Serum C3 and C4 are acute phase proteins, she notes, yet these tests have limited sensitivity and specificity. Therefore, trajectory and repeated measurements are helpful. She also talks about functional assessments of complement proteins and measurements of autoantibodies to complement proteins. She notes that some tests explore fragments in urine but these are not standardized. She also notes tests of the complement system in the tissue phase, noting it is difficult to test for C3, which can be negatively or mildly positive in well defined cases of DDD, or result in false positive tests.
0:42:00 - The role of complement in kidney disease
Dr. Dokouhaki notes that the complement system is increasingly being associated with kidney diseases. She highlights the role of the complement system in ANCA associate vasculitis, and cites preclinical studies showing that C5-deficiency or C5R inhibition were found to be protective, as well as some subsequent clinical trials resulting in FDA approval. Next, she talks about IgA nephropathy and the complement system, where it helps break down immune complexes but these can accumulate in the kidney; ironically, if a patient doesn’t have complement activity it can cause both problems and be helpful, she notes.
0:52:00 - Complement therapeutics
She briefly highlights complement therapies that have been approved for kidney-related complications, as well as numerous drugs currently in the pipeline.
0:53:00 - Questions from the Audience
Dr. Dokouhaki takes questions from the audience.
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