Molecular Identification of Pathogenetic IdLNF+1 Autoantibody Idiotypes Derived from the (NZB×SWR)F1 Model for Systemic Lupus Erythematosus

Immunization with peptides derived from the idiotypic region of lupus-associated autoantibodies delays the development of lupus nephritis in the (SWR×NZB)F1 murine model

“…Price et al [17] tested several of the 65 monoclonal antibodies isolated by Gavalchin et al [13] for the ability to stimulate T-cells derived from nephritic SNF 1 females, as well as T-cell clones that where isolated based upon their reactivity with Id LN F 1 [6]. One Id LN F 1 þ antibody, designated 540, significantly stimulated both the syngeneic T-cells and the T-cell clones and also caused nephritis when injected as a hybridoma into non-autoimmune (Balb/c  SWR)F 1 mice.…”

“…The variable region of the heavy chain of 540 was sequenced, and peptides derived from its sequence were tested for the ability to induce the proliferation of the T-cell clones as well as of splenic T-cells derived from nephritic SNF 1 mice. Two over-lapping peptides from the heavy chain variable region, amino acids 54e66 (KDGTKYNEKFKGK) and 62e73 (KFKGKATLTSDK), were found to contain the peptide ligand for the Id LN F 1 -reactive T-cell clones and the splenic-derived T-cells [17].…”

Novel, orally active, proteasome inhibitor, delanzomib (CEP-18770), ameliorates disease symptoms and glomerulonephritis in two preclinical mouse models of SLE

“…Bortezomib reversibly inhibits the chymotrypsin-like activity of the proteasome and is an approved proteasome inhibitor for the treatment of patients with multiple myeloma and mantle cell lymphoma and is currently in a Phase IV for the treatment of lupus nephritis patients (www.clinicaltrials.gov) [23]. In preclinical mouse models bortezomib has shown efficacy in the treatment of RA [24] and SLE [12].…”

Accelerated Macrophage Apoptosis Induces Autoantibody Formation and Organ Damage in Systemic Lupus Erythematosus

“…SNF 1 mice develop a lupus like-disease with autoantibody formation and severe nephritis (15). DBF 1 were used as non-autoimmune haplotype-matched controls, which do not develop lupuslike features (15). Protocol was reviewed and approved by the University of Michigan's Committee on Use and Care of Animals.…”

“…The F 1 progeny of NZB ϫ SWR (SNF 1 ) and BALB/c ϫ DBA1 (DBF 1 ) mice were bred and aged at the State University of New York Upstate Medical University at Syracuse, Department of Laboratory Animal Resources, and shipped to the Unit of Laboratory Animal Medicine, University of Michigan, where they were housed in a specific pathogen-free facility. SNF 1 mice develop a lupus like-disease with autoantibody formation and severe nephritis (15). DBF 1 were used as non-autoimmune haplotype-matched controls, which do not develop lupuslike features (15).…”