Immune Deposits, Complement Activation, and APOL1 Risk Variants in Focal Segmental Glomerulosclerosis.
Yasar Caliskan1,2, Virginie Royal3, Stéphan Troyanov4
1Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee, USA, yasar.caliskan@vumc.org.
American Journal of Nephrology
|February 19, 2026
Summary
APOL1 high-risk FSGS is linked to immune deposits and complement activation. This suggests immune-mediated pathways contribute to FSGS development in high-risk individuals.
Area of Science:
- Nephrology
- Immunology
- Genetics
Background:
- The role of immune deposits and complement activation in APOL1-mediated focal segmental glomerulosclerosis (FSGS) is not fully understood.
- Investigating these factors is crucial for understanding FSGS pathogenesis.
Purpose of the Study:
- To examine the associations between APOL1 renal risk variants (RRVs), glomerular immune deposits, and urinary complement activation in FSGS patients.
- To clarify the immune-mediated mechanisms in APOL1-associated FSGS.
Main Methods:
- Analysis of glomerular IgG, IgM, and C3 deposition, kidney biopsy findings, and urinary membrane attack complex (sC5b9) levels in 175 FSGS patients.
- Categorization of participants into high-risk (two RRVs) and low-risk (zero to one RRV) groups based on genetic testing.
Main Results:
- High-risk participants showed a higher prevalence of collapsing FSGS and mesangial IgG deposition compared to low-risk individuals.
- A trend towards higher urinary sC5b9 levels was observed in high-risk participants.
- Glomerular IgG staining significantly correlated with urinary sC5b9 levels, indicating a link between IgG deposition and complement activation.
Conclusions:
- APOL1 high-risk FSGS is associated with specific immune deposit patterns (mesangial IgG) and elevated urinary complement activation markers.
- These findings implicate immune-mediated mechanisms in the pathogenesis of FSGS among individuals with APOL1 risk variants.
More Related Videos
06:39Glomerular Outgrowth as an Ex Vivo Assay to Analyze Pathways Involved in Parietal Epithelial Cell Activation
Published on: August 19, 2020
5.0K
09:43Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
2.6K
Related Concept Videos
03:03Amyloid Fibrils
10.2K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
10.2K
01:20Renal Corpuscle
8.3K
The glomerulus and Bowman's capsule are two essential components of the nephron, which is the functional unit of the kidney. These microscopic structures play a critical role in the process of blood filtration to produce urine.
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...
8.3K
01:27Complement System
10.5K
The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
10.5K
01:24Nephrotic Syndrome I : Introduction
1.1K
Nephrotic Syndrome is a chronic kidney disorder defined by clinical findings such as severe proteinuria, hypoalbuminemia, hyperlipidemia, and edema. These symptoms result from damage to the glomeruli, the kidney’s filtering units, increasing their permeability to proteins.Definition and Meaning:Proteinuria, defined as the loss of more than 3.5 grams of protein per day in adults, is a crucial feature of nephrotic syndrome. This condition is often accompanied by edema, the accumulation of...
1.1K
01:28Diabetic Nephropathy
28
Definition Diabetic nephropathy is a chronic kidney complication that results from prolonged hyperglycemia.Prevalence It is the most common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide, affecting up to half of individuals with diabetes.Pathophysiology • Sustained hyperglycemia triggers multiple hemodynamic and metabolic changes in the kidney. • Early in the disease, increased renal blood flow and glomerular hyperfiltration...
28
01:29Alzheimer Disease l: Introduction
20
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
20