Systemic Lupus Erythematosus (SLE)
SLE is a chronic autoimmune disorder, characterized by numerous anti-nuclear autoantibodies, systemic inflammation and lymphopenia as a consequence of an impaired immune system.
At Invivocue, we have successfully recapitulated most of the hallmark of clinical and immunological features of SLE by single pristane induction in B-cell enhanced HiMice.
Cytokines, autoantibodies and T-B cells responses in this SLE model are human-specific. Hence, it provides an exclusive in-vivo platform for the study of disease pathogenesis, as well as immunotherapeutic target identification and drug evaluation.
Key Features
Consistent, sustained increase in dsDNA IgG levels over 12 weeks post-pristane administration.
Robust and improved myeloid cell reconstitution with increased granulocytes and monocyte levels.
Highly responsive to Rituximab, a B-cell depleting treatment, demonstrating the translational validity of this model.
Improved survivability of B cells following pristane injection, allowing testing of B-cell depletion therapies.
Sufficient levels of T-cells allow for reprogramming modalities to be tested.
Figure: Establishment and features of humanized SLE model.
DATA
Immune Cell Profiling before and after Pristane Injection
Humanized mice continue to develop the whole spectrum of immune cells even after pristane injection.
Antinuclear Autoantibody Quantification
1. The positive index value is a relative measure of the amount of dsDNA levels compared to a control group. The positive index value is calculated as (net sample OD) divided by (2 SD of the control group + the mean OD of control)dsDNA levels (positive index value)1 increase over time in SLE mice.
This trend sustains for at least 12 weeks post Pristane injection.
anti-CD20 cell-depleting antibody (Rituximab) demonstrates and validates the role of these cells in pathogenesis of SLE
This model is suitable for drug efficacy studies owing to this translational validity.
Kidney Histopathology
Pristane administration leads to the thickening of the glomerular basement membrane, glomerular hypercellularity, and significant deposition of IgG in the kidney, which is a hallmark of Lupus nephritis.
Following 12 weeks of treatment with Rituximab, significant reduction in glomerular hyperproliferation and IgG deposition events were observed and consistent with the levels of dsDNA antibody in plasma. The staining results demonstrated a strong correlation between the effectiveness of Rituximab treatment and the severity of renal manifestations in the Lupus nephritis model.
Given the complexity of human disease, in-depth knowledge of each model is key to success in pre-clinical studies. Invivocue offers tailor-made study designs to suit your research needs.