Down-regulation of surface antigens recognized by systemic lupus erythematosus antibodies on embryonal cells following differentiation and exposure to corticosteroids

Putterman, Chaim; Ulmansky, Rina; Rasooly, Linda; Tadmor, Boaz; Ben-Bassat, Hanna; Naparstek, Yaakov

doi:10.1002/(sici)1521-4141(199805)28:05<1656::aid-immu1656>3.0.co;2-5

Cited by 5 publications

(3 citation statements)

References 15 publications

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“…We previously reported that monoclonal mouse and polyclonal human anti-dsDNA Abs from lupus patients bind to the cell surface of mouse embryonic stem cells. This cell surface receptor was markedly down-regulated by a brief pretreatment of cells with dexamethasone, leading to a Ͼ50% decrease in Ab binding (38). Based on these results, we had postulated that while corticosteroids have many anti-inflammatory and immunosuppressive effects, modulation of target Ag can be invoked as an additional explanation for the therapeutic benefit of steroids in lupus nephritis.…”

Section: Discussionmentioning

confidence: 94%

Differential Binding of Cross-Reactive Anti-DNA Antibodies to Mesangial Cells: The Role of α-Actinin

Zhao

Deocharan

Scherer

et al. 2006

The Journal of Immunology

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Target Ag display is a necessary requirement for the expression of certain immune-mediated kidney diseases. We previously had shown that anti-DNA Abs that cross-react with α-actinin may be important in the pathogenesis of murine and human lupus nephritis; in murine models, we had found that a significant proportion of pathogenic serum and kidney-deposited Igs are α-actinin reactive. Furthermore, a pathogenic anti-DNA/α-actinin Ab showed enhanced binding to immortalized mesangial cells (MCs) derived from a lupus prone MRL-lpr/lpr mouse as compared with MCs from BALB/c mice which are not susceptible to spontaneous lupus, suggesting that kidney α-actinin expression may be contributing to nephritis. In the current study, we established that two isoforms of α-actinin that are present in the kidney, α-actinin 1 and α-actinin 4, can both be targeted by anti-α-actinin Abs. We found novel sequence polymorphisms between MRL-lpr/lpr and BALB/c in the gene for α-actinin 4. Moreover, α-actinin 4 and a splice variant of α-actinin 1 were both expressed at significantly higher levels (mRNA and protein) in MCs from the lupus prone MRL-lpr/lpr strain. Significantly, we were able to confirm these differences in intact kidney by examining glomerular Ig deposition of anti-α-actinin Abs. We conclude that enhanced α-actinin expression may determine the extent of Ig deposition in the Ab-mediated kidney disease in lupus. Modulation of Ag expression may be a promising approach to down-regulate immune complex formation in the target organ in individuals with circulating pathogenic Abs.

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Section: Discussionmentioning

confidence: 94%

Differential Binding of Cross-Reactive Anti-DNA Antibodies to Mesangial Cells: The Role of α-Actinin

Zhao

Deocharan

Scherer

et al. 2006

The Journal of Immunology

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“…23 Other mechanisms include the binding of antibodies found in SLE to membrane antigens on the surface of the embryonal cells. 24 The most important autoantibodies present in SLE are the anti-DNA antibodies, which are found in almost every patient and are of diagnostic importance in SLE. The mechanism by which these autoantibodies leads to the damage observed in lupus patients as well as their effects on reproduction has not been clarified.…”

Section: Discussionmentioning

confidence: 99%

Anti‐DNA Antibodies Cross‐reacting with Laminin Inhibit Trophoblast Attachment and Migration: Implications for Recurrent Pregnancy Loss in SLE Patients

Qureshi

Yang²,

Jaques³

et al. 2000

American J Rep Immunol

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“…Similarly, we have demonstrated that monoclonal mouse and polyclonal human anti-dsDNA antibodies bind to the cell surface of undifferentiated mouse embryonic stem cells. 48 However, when these cells are allowed to differentiate, binding is signi cantly reduced. Furthermore, we have shown that a pathogenic anti-dsDNA antibody preferentially binds to glomeruli of BALB = c mice as compared with C57BL = 6 mice.…”

Section: The Cross-reactive Renal Target For Anti-dsdna Antibodiesmentioning

confidence: 99%

Antigenic triggers and molecular targets for anti-double-stranded DNA antibodies

Deocharan¹,

Qing

Beger

et al. 2002

Lupus

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While anti-double-stranded (ds)DNA antibodies are a characteristic serologic hallmark for SLE, the triggering antigen is unknown. Using phage display libraries, we identified DWEYSVWLSN as a peptide mimic of DNA for a pathogenic anti-dsDNA antibody. Peptide immunization of non-autoimmune mice induced anti-dsDNA as well as other lupus-associated antibodies. Molecular analysis of the induced anti-dsDNA antibodies revealed several similarities with anti-dsDNA antibodies that appear spontaneously in lupus mice. Furthermore, lupus-prone mice immunized with this peptide DNA mimic had higher autoantibody titers as well as more severe nephritis. Anti-DNA antibodies may contribute to lupus nephritis via cross-reactivity with renal antigen. Using western blotting of lysates of mesangial cells from a lupus mouse, we found that a pathogenic anti-DNA antibody binds to alpha-actinin. High titers of anti-alpha-actinin antibodies were present in the sera and kidney eluates of lupus mice with active disease. Binding to alpha-actinin was diminished in mesangial cells derived from BALB/c mice, suggesting that target antigen expression may play a role in determining autoantibody binding to the kidney. We conclude that a pathogenic, lupus-like autoantibody response can be induced by a peptide antigen, and that alpha-actinin is a cross-reactive renal target for the pathogenic anti-dsDNA autoantibody response in lupus mice.

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Down-regulation of surface antigens recognized by systemic lupus erythematosus antibodies on embryonal cells following differentiation and exposure to corticosteroids

Cited by 5 publications

References 15 publications

Differential Binding of Cross-Reactive Anti-DNA Antibodies to Mesangial Cells: The Role of α-Actinin

Differential Binding of Cross-Reactive Anti-DNA Antibodies to Mesangial Cells: The Role of α-Actinin

Anti‐DNA Antibodies Cross‐reacting with Laminin Inhibit Trophoblast Attachment and Migration: Implications for Recurrent Pregnancy Loss in SLE Patients

Antigenic triggers and molecular targets for anti-double-stranded DNA antibodies

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