Abstract: TH-PO824
A Humanized Mouse Model of SLE and LN
Session Information
- Glomerular Diseases: Immunology and Inflammation - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Khan, Samia Qamar, Rush University Medical Center, Chicago, Illinois, United States
- Li, Xiaobo, Rush University Medical Center, Chicago, Illinois, United States
- Wei, Huiting, Rush University Medical Center, Chicago, Illinois, United States
- Hahm, Eunsil, Rush University Medical Center, Chicago, Illinois, United States
- Jolly, Meenakshi, Rush University Medical Center, Chicago, Illinois, United States
- Gupta, Vineet, Rush University Medical Center, Chicago, Illinois, United States
Background
Lupus Nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) with unclear etiology and limited treatment options. Single Nucleotide Polymorphisms (SNPs) in ITGAM (which codes for CD11b) strongly associate with disease pathogenesis. Yet, the role of these mutations in disease pathobiology is unclear, primarily because of a lack of experimental models. Additionally, while available spontaneous or induced mouse models of SLE have advanced our understanding of lupus, none of them replicate human disease very well. Here, we present a novel humanized mouse model of SLE and LN that better mimics the human disease and, we hope, will greatly improve our understanding of the cellular and genetic determinants driving lupus and aid in the development of novel therapeutics.
Methods
Peripheral blood mononuclear cells (PBMCs) were transferred from healthy donors or SLE patients into NSG mice (Healthy-NSG and SLE-NSG). Weekly blood and urine samples were collected and humanized mice were monitored for lupus symptoms until end-point at 6-weeks post engraftment when they were sacrificed and tissues, serum and blood were harvested for further analysis.
Results
Using our optimized protocol, the engraftment of healthy and SLE PBMCs was 100% successful in the NSG mice. We observed an average of 78% human CD45+ cells in the spleens at 6 weeks post engraftment. Interestingly, mouse CD11b+Gr1+ cells and human CD14+ cells were significantly elevated in vivo in SLE-NSG mice as compared to healthy-NSG mice. Within 1 week, SLE-NSG mice also lost whiskers and developed alopecia. Histopathological analysis of nasal dermis showed increased epidermal thickness and leukocyte density. Similar to human PBMC donors that displayed renal decline, SLE-NSG mice also showed significantly elevated levels of serum anti-dsDNA and suPAR, and significantly reduced kidney function, as indicated by elevated levels of proteinuria, renal leukocyte infiltration, renal fibrosis and glomerular damage.
Conclusion
This novel humanized SLE/LN model exhibits several clinical manifestations of human lupus and is an important tool to test therapies.
Funding
- Other NIH Support