Variable region sequences of autoantibodies from mice with experimental systemic lupus erythematosus

Waisman, Ari; Mozes, Edna

doi:10.1002/eji.1830230726

Cited by 33 publications

(10 citation statements)

References 44 publications

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“…Moreover, Abs with a heavy chain encoded by this J558 family member have been demonstrated to be pathogenic. Interestingly, V H BW-16 encoded heavy chains have also been recently identified in several models of experimental anti-dsDNA responses in nonautoimmune mice (35,36). Eilat et al studied the characteristics of Abs using V H BW-16-encoded heavy chains in nonautoimmune mice with an induced anti-dsDNA response and in diseased (NZB ϫ NZW)F 1 mice (24).…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of the Autoantibody Response in Peptide-Induced Autoimmunity

Putterman

Deocharan

Diamond

2000

The Journal of Immunology

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Immunization of nonautoimmune BALB/c mice with multimeric DWEYSVWLSN, a peptide mimotope of DNA, induces anti-DNA and other lupus-associated Abs. To further investigate the pathogenesis of the autoantibody response induced by peptide immunization, we generated hybridomas from peptide-immunized mice that bound peptide, dsDNA, cardiolipin, Sm/ribonucleoprotein (RNP), or some combination of these Ags. Analysis of 24 IgM Abs led to the identification of three groups of Abs: 1) Abs reactive with peptide alone, 2) anti-peptide Abs cross-reactive with one or more autoantigens, and 3) autoantibodies that do not bind to peptide. The gene families and particular VH-VL combinations used in those hybridomas binding DNA were similar to those used in the anti-DNA response in spontaneous murine lupus. Another similarity to the spontaneous anti-DNA response was the generation of arginines in the complementarity-determining region-3 of DNA-binding hybridomas. Interestingly, one Ab had the VH-VL combination present in the original R4A anti-DNA Ab used to select the DWEYSVWLSN peptide from a phage display library. Many of the heavy and light chains displayed evidence of somatic mutation, suggesting that they were made by Ag-activated B cells. Analysis of the Ab repertoire in peptide-induced autoimmunity may provide insights into the generation of anti-DNA Abs following exposure to foreign Ag. Furthermore, the recovery of an Ab with the heavy and light chain combination of the Ab originally used to isolate the immunizing peptide confirms the utility of phage display peptide libraries in generating true molecular mimics.

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Section: Discussionmentioning

confidence: 99%

Molecular Analysis of the Autoantibody Response in Peptide-Induced Autoimmunity

Putterman

Deocharan

Diamond

2000

The Journal of Immunology

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“…Experimental SLE, although induced in mice that normally do not develop any symptoms of SLE, was found to share features with (NZB ϫ NZW)F 1 mice that develop the disease spontaneously. Thus, we have demonstrated high homology between the variable regions coding for the heavy and light chains of anti-DNA mAb isolated from mice afflicted with experimental SLE and the variable regions of anti-DNA mAb from (NZB ϫ NZW)F 1 mice (7).…”

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confidence: 90%

Modulation of murine systemic lupus erythematosus with peptides based on complementarity determining regions of a pathogenic anti-DNA monoclonal antibody

Waisman

Ruiz

Israeli

et al. 1997

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

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Experimental systemic lupus erythematosus (SLE) can be induced in naive mice by immunization with a murine monoclonal anti-DNA antibody (mAb), 5G12, that bears a major idiotype designated 16͞6 Id. Strain-dependent differences were observed in the proliferative responses of lymph node cells of mice immunized with two peptides based on the sequences of the complementarity determining region (CDR) 1 and 3 of mAb 5G12. The capacity of the peptides to bind to major histocompatibility complex class II molecules correlated with the proliferative responses. Immunization of high responder strains with the CDR-based peptides led to production of autoantibodies and clinical manifestations characteristic to experimental SLE. The CDR-based peptides could prevent autoantibody production in neonatal mice that were immunized later either with the peptide or with the pathogenic autoantibody. Furthermore, the peptides inhibited specific proliferation of lymph node cells of mice immunized with the same peptide, with mAb 5G12 or with the human mAb anti-DNA, 16͞6 Id. Thus, the CDR-based peptides are potential candidates for therapy of SLE.

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“…leukopenia, thrombocytopenia and renal impairment) [6–8]. Autoantibodies isolated from the diseased mice including the 5G12 MoAb were shown to be highly homologous to anti‐DNA MoAb isolated from the SLE‐prone (NZB × NZW)F1 mice [9], supporting further the importance of the 16/6 Id in SLE.…”

Section: Introductionmentioning

confidence: 98%

Modulation of autoreactive responses of peripheral blood lymphocytes of patients with systemic lupus erythematosus by peptides based on human and murine anti-DNA autoantibodies

Sthoeger

Dayan

Tcherniack

et al. 2003

Clinical and Experimental Immunology

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SUMMARYTwo peptides, based on the sequences of the complementarity-determining regions (CDR) 1 and 3 of a pathogenic murine monoclonal anti-DNA autoatibody that bears the 16/6 idiotype (Id), were shown to either prevent or treat an already established systemic lupus erythematosus (SLE) in two murine models of lupus. Two additional peptides based on the human monoclonal anti-DNA, 16/6 Id were synthesized. This study was undertaken in order to investigate the ability of the CDR-based peptides to immunomodulate SLE-associated responses of peripheral blood lymphocytes (PBL) of SLE patients. PBL of 24 of the 62 SLE patients tested proliferated in vitro following stimulation with the human 16/ 6 Id. Peptides based on the CDRs of both the human and murine anti-DNA autoantibodies inhibited efficiently and specifically the 16/6 Id-induced proliferation and IL-2 production. The latter inhibitions correlated with an up-regulated production (by 2·5-3·5-fold) of the immunosuppressive cytokine, TGFb . Overall, the results of our study demonstrate that the CDR-based peptides are capable of down-regulating in vitro autoreactive T cell responses of PBL of SLE patients. Thus, these peptides are potential candidates for a novel specific treatment of SLE patients.

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Variable region sequences of autoantibodies from mice with experimental systemic lupus erythematosus

Cited by 33 publications

References 44 publications

Molecular Analysis of the Autoantibody Response in Peptide-Induced Autoimmunity

Molecular Analysis of the Autoantibody Response in Peptide-Induced Autoimmunity

Modulation of murine systemic lupus erythematosus with peptides based on complementarity determining regions of a pathogenic anti-DNA monoclonal antibody

Modulation of autoreactive responses of peripheral blood lymphocytes of patients with systemic lupus erythematosus by peptides based on human and murine anti-DNA autoantibodies

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