Binding of cytoskeletal proteins by monoclonal anti-DNA lupus autoantibodies

André-Schwartz, J; Datta, Somnath; Schoenfeld, Y; Isenberg, David; Stollar, B. David; Schwartz, Robert S.

doi:10.1016/0090-1229(84)90246-0

Cited by 152 publications

(35 citation statements)

References 27 publications

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“…The major location of ␣-actinin, as an important cytoskeletal component, is intracellular. It has already been known for some time that SLE patients display Abs to cytoskeletal proteins (21,22) and microfilaments (23), including Abs to ␣-actinin. Nevertheless, here we confirm earlier observations (10,11,18) that ␣-actinin is also present on the cell surface, where it is accessible for Ab binding in vivo.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…Polyspecificity has also been reported in some IgG mAbs . An IgG anti-DNA mAb has been shown to bind to vimentin (21) and another IgG2b anti-DNA mAb was found to bind to renal mesangium and vascular endothelium (22), which resulted in an increase in albumin permeability in perfused rat kidneys.…”

Section: Discussionmentioning

confidence: 99%

Autoimmune mice make anti-Fc gamma receptor antibodies.

Boros

Chen

Bona

et al. 1990

The Journal of Experimental Medicine

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Hallmarks of autoimmune diseases such as SLE are hypergammaglobulinemia, the production of autoantibodies, and elevated levels of circulating immune complexes . Several mouse strains are used as models of SLE (see reference 1 for review), including NZB, NZB/NZW Ft , MRL/lpr, and BXSB . In human and murine SLE, there is frequently a .pronounced inhibition of macrophage binding and phagocytosis of IgG-sensitized erythrocytes and immune complexes (2-4) . One possible reason for this inhibition is the downmodulation of the macrophage Fcy R after binding of immune complexes . An alternate explanation for the inhibition of Fc yR function might be the binding of anti-Fcy R autoantibody to the macrophage FcyR .In this study, we have used a recombinant truncated FcyR (tFcyR) t to screen murine sera and mAbs for naturally occurring anti-Fcy R antibody. The tFcyR is derived from murine FcyRIIf, and consists of the two external Ig-like domains of muFcy RIIa, but lacks the transmembrane and cytoplasmic domains of the receptor (5) . We report here the presence and characterization of anti-Fcy R antibodies in sera ofsome mice genetically prone to autoimmune diseases and anti-Fc yR hybridomas derived from NZB and motheaten (me") mice.Volume 171 May 1990 1581-1595 AUTOIMMUNE MICE MAKE ANTI-Fcy RECEPTOR ANTIBODIES Materials and Methods mAbs and Sera. The mAbs that we screened for anti-FcyR activity were derived from fusions with spleen cells from old NZB mice or young NZB mice after stimulation with LPS (6) . Other hybridomas screened were from unstimulated viable me' mice (7) . The IgM mAbs were all purified by affinity chromatography on an anti-tc IgG-Sepharose column and were eluted from the column with 0 .1 M glycine HCI, pH 2 .3 . Samples of sera from NZB, NZB/NZW F,, MRL/lpr, and BXSB mice were kindly given to us by Dr. Argyris Theofilopoulos (Scripps Clinic, La Jolla, CA) . Sera from me', tightskin mouse (TSK), C57B1 .6pa/pa, and C58/J were obtained from animals purchased from The Jackson Laboratory (Bar Harbor, ME). Anti-DNP hybridomas DHK109 .3 (IgGl) and DHK10 .12 (IgG2b)

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“…which s h o w cytoskeleta1 staining and react with nucleic acid antigens a n d / o r cardiolipin, appear to be similar to t h e monoclonal a n t i -D N A antibodies of SLE origin (13). The similar antigen-binding properties of t h e SLE and normal anti-DNA autoantibodies provide further evidence for t h e qualitative similarities of t h e s e autoantibodies in SLE patients a n d in normal subjects.…”

Section: Discussionmentioning

confidence: 60%

“…The cytoskeletal reactivity of monoclonal anti-DNA antibodies derived from hybridomas of SLE of human and murine origin has been reported (13 (20). The high degree of structural homology present in the central a helical coiled core, which exists in all types of intermediate filaments (21), may also be responsible for the anti-vimentin reactivity in these epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

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Cytoskeletal binding of monoclonal anti‐dna antibodies derived from tonsillar lymphoid cells of a normal subject

Cairns

Komar

Bell

1986

Arthritis & Rheumatism

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The ability of monoclonal IgM anti‐DNA auto‐antibodies derived from normal human lymphoid cells to bind to cellular constituents of human epithelial cells (HEp‐2) was examined by immunofluorescence. Hybridoma supernatants from 10 different clones were studied. Four of them gave a strong fibrillar cytoplasmic staining that resembled cytoskeletal staining, 1 showed strong nuclear staining only, 3 showed weak nucleolar staining only, and 2 showed no staining. The hybridoma supernatants that reacted with HEp‐2 cytoskeleton were either polyspecific for various nucleic acid antigens, such as single‐stranded DNA, DNA, poly(dA:dT), poly(dG)·poly(dC), RNA, and cardiolipin, or were restricted to cardiolipin. Cytoskeletal staining identical to the hybridoma supernatant staining was also seen with mouse monoclonal anti‐vimentin antibody B11.5.1. Inhibition of the cytoskeletal staining was accomplished in 3 of the 4 hybridoma supernatants by preabsorption of these hybridoma supernatants with cardiolipin and/or single‐stranded DNA, or by preincubation of the HEp‐2 cells with the mouse monoclonal anti‐vimentin antibody.

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Binding of cytoskeletal proteins by monoclonal anti-DNA lupus autoantibodies

Cited by 152 publications

References 27 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

Autoimmune mice make anti-Fc gamma receptor antibodies.

Cytoskeletal binding of monoclonal anti‐dna antibodies derived from tonsillar lymphoid cells of a normal subject

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