After left nephrectomy, 3 10-week old NZB/W mice received orthotopic grafts of kidneys from parental NZW mice of the same age. At autopsy conducted at the age of 33-38 weeks, glomerulonephritis of similar extent was noted in the recipients' own and in the grafted kidneys. Also, very similar granular deposits of immunoglobulins and complement were demonstrated in these kidneys. It was concluded that the absence of glomerulonephritis in NZW mice cannot be attributed to the refractoriness of their kidney to this disease.
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http://dx.doi.org/10.1159/000235521 | DOI Listing |
Arthritis Rheumatol
July 2023
Alpine Immune Sciences, Inc., Seattle, Washington.
Objective: Dysregulated APRIL/BAFF signaling is implicated in the pathogenesis of multiple autoimmune diseases, including systemic lupus erythematosus and lupus nephritis. We undertook this study to develop and evaluate a high-affinity APRIL/BAFF antagonist to overcome the clinical limitations of existing B cell inhibitors.
Methods: A variant of TACI-Fc generated by directed evolution showed enhanced binding for both APRIL and BAFF and was designated povetacicept (ALPN-303).
Arthritis Rheumatol
August 2022
University of Rochester Medical Center, Rochester, New York.
Objective: To investigate the hypothesis that selective inhibitors of nuclear export (SINE compounds), recently approved for treatment of refractory plasma cell (PC) malignancy, may have potential in the treatment of lupus.
Methods: Female NZB/NZW mice were treated with the SINE compound KPT-350 or vehicle control. Tissue specimens were harvested and analyzed by flow cytometry, using standard markers.
Front Immunol
September 2021
Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase mediating trimethylation of H3K27, which represses gene expression and is critical to immune regulation. Inhibition of EZH2 is proved to have the potential of treating many diseases. However, whether inhibition of EZH2 affects type I interferon (IFN-I) signaling pathway, the abnormality of which is an important pathogenic mechanism for SLE, is still elusive.
View Article and Find Full Text PDFArthritis Rheumatol
August 2021
Medical University of South Carolina, Charleston.
Objective: To examine the therapeutic effects of camptothecin (CPT) and topotecan (TPT), inhibitors of transcription factor Fli-1 and topoisomerase, on lupus nephritis in (NZB × NZW)F1 (NZBWF1) mice, and to examine the effects of CPT and TPT on inflammatory mediators in human renal cells.
Methods: Female NZBWF1 mice were treated with vehicle, cyclophosphamide (CYC), CPT (1 mg/kg or 2 mg/kg), or TPT (0.03 mg/kg, 0.
Clin Immunol
March 2021
Division of Rheumatology, Center for Immunity, Inflammation and Regenerative Medicine, Charlottesville, VA, USA; Department of Medicine, University of Virginia, Charlottesville, VA, USA; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA. Electronic address:
Cgnz1 on chromosome 1 mapped into a 1.34 Mb region of chromosome 1 in NZM2328 confers the progression of immune complex (IC)-mediated glomerulonephritis (GN) from acute GN (aGN) to chronic GN (cGN) with severe proteinuria and end stage renal disease in female mice. This genetic locus mediates podocyte susceptibility to IC-mediated damage.
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