RETRACTED: A novel pseudovirus encoding Diphtheriatoxin A fragment eliminates autoantibody-producing B cells and inhibits lupus in the BWF1 mouse model

H, Tan; Xiong, Yijun; She-huai, Cui; Yang, Zhao

doi:10.1016/j.imlet.2009.07.011

Cited by 1 publication

(1 citation statement)

References 26 publications

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“…This reagent decreased titers of anti-dsDNA antibodies and improved renal survival in MRL/lpr mice. An additional study described the effects of incorporating the DWEYS peptide and diphtheria toxin A into a pseudovirus; this reagent reduced anti-dsDNA antibodies and improved survival in NZB/W mice (36). These studies showed that it may not be necessary to target all anti-dsDNA antibodies to achieve a therapeutic effect.…”

Section: Discussionmentioning

confidence: 99%

Generation of a unique small molecule peptidomimetic that neutralizes lupus autoantibody activity

Bloom

Cheng

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of pathogenic autoantibodies, many of which are directed against nuclear antigens, in particular double-stranded (ds) DNA. Both clinical studies and animal models have shown that anti-dsDNA antibodies contribute to kidney disease, which is present in 50% of lupus patients and is a major cause of mortality. We previously demonstrated that a subset of nephrotoxic anti-dsDNA antibodies also recognizes the pentapeptide consensus sequence D/E W D/E Y S/G (DWEYS) present in the NR2A and NR2B subunits of the N -methyl- d -aspartate receptor (NMDAR). Autoantibodies with this specificity are present in ≈40% of lupus patient sera and are both nephrotoxic and neurotoxic. Elevated titers are present in cerebrospinal fluid of patients with central nervous system manifestations of SLE. Administration of the nonnaturally occurring D form of the DWEYS pentapeptide prevents these antibodies from depositing in glomeruli and from mediating neuronal excitotoxicity. To craft a more useful therapeutic, we used the structural features of the DWEYS peptide to design a unique, selective, and potent small molecule peptidomimetic, FISLE-412, which neutralizes anti-dsDNA/NMDAR lupus autoantibodies and prevents their pathogenic interaction with tissue antigens. This compound, or others derived from it, may provide a unique strategy for the development of lupus therapeutics.

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Section: Discussionmentioning

confidence: 99%