Systemic Lupus Erythematosus (SLE)
SLE is a chronic autoimmune disorder, characterized by numerous anti-nuclear autoantibodies, series of systemic and organs inflammation and lymphopenia as a consequence of 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.
Figure: Establishment and features of humanized SLE model.
Key features observed:
Increase of human autoantibodies
Lupus nephritis
Lymphopenia
Hyperactivation of B and T cells
Activation of Pro-inflammatory cytokines
DATA
Antinuclear Autoantibody Quantification
Mice treated with either Rituximab (a B cells inhibitor) or Cyclophosphamide (immunosuppressive drugs) showed a significant reduction in plasmatic dsDNA levels compared to the control group treated with saline at week 12 following pristane injection.
Immune Analysis
Lymphopenia was observed pristane treated mice (control). Administration of Rituximab and cyclophosphamide effectively depleted the B cells and total lymphocytes in peripheral blood.
Histopathology Analysis on Kidney
The administration of Pristane led 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 ds-DNA antibody in the 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.