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Updated: Mar 6, 2026
The bm12 Inducible Model of Systemic Lupus Erythematosus SLE in C57BL/6 Mice
Published on: November 1, 2015
ApoL1 and the Immune Response of Patients with Systemic Lupus Erythematosus
Ashira D Blazer1, Robert M Clancy2
1Division of Rheumatology, Department of Medicine, New York University School of Medicine, 550 First Avenue, MSB 611, New York, NY, 10016, USA. ashira.blazer@nyumc.org.
Insights
Genetic variations in the apolipoprotein L1 (APOL1) gene are linked to cardiovascular disease (CVD) risk in systemic lupus erythematosus (SLE). Divergent APOL1 pathways may explain worsened outcomes in SLE patients, particularly African Americans.
Area of Science:
- Genetics
- Immunology
- Cardiovascular Medicine
Background:
- Systemic lupus erythematosus (SLE) significantly elevates cardiovascular disease (CVD) risk, especially in African Americans.
- APOL1 gene variations at 22q13 are associated with kidney disease and CVD.
Purpose of the Study:
- To investigate the role of APOL1 gene variations in the heightened cardiovascular risk observed in SLE.
- To explore how APOL1's altered intracellular pathways contribute to disease severity in SLE.
Main Methods:
- Genome-wide association studies (GWAS) identified the APOL1 locus.
- Analysis of structure-functional differences between ancestral and variant APOL1 forms.
- Examination of APOL1's impact on cellular autophagy and pore-forming activity.
Main Results:
- APOL1 variations are linked to progressive nondiabetic nephropathy, CVD, and lupus nephritis.
- Variant APOL1 exhibits a toxic gain of function, attenuating autophagy.
- Variant APOL1 possesses unsupervised pore-forming capabilities, unlike ancestral APOL1.
Conclusions:
- Altered intracellular APOL1 pathways, driven by genetic variations, may underlie the increased CVD risk and severity in SLE.
- Divergent biological functions of ancestral versus variant APOL1 explain worsened prognoses in SLE.
Purpose Of Review:
Systemic lupus erythematosus (SLE) confers up to a 50-fold increased risk of cardiovascular disease (CVD), and African Americans with SLE experience accelerated damage accrual and doubled cardiovascular risk when compared to their European American counterparts.
Recent Findings:
Genome-wide association studies have identified a substantial signal at 22q13, now assigned to variation at apolipoprotein L1 (APOL1), which has associated with progressive nondiabetic nephropathy, cardiovascular disease, and many immune-associated renal diseases, including lupus nephritis. We contend that alterations in crucial APOL1 intracellular pathways may underpin associated disease states based on structure-functional differences between variant and ancestral forms. While ancestral APOL1 may be a key driver of autophagy, nonconserved primary structure changes result in a toxic gain of function with attenuation of autophagy and an unsupervised pore-forming feature. Thus, the divergent intracellular biological pathways of ancestral and variant APOL1 may explain a worsened prognosis as demonstrated in SLE.
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