Crossreactivity of Monoclonal Antibodies to DNA: Related to Avidity?

Smeenk, R. J. T.; Westgeest, Toon; Duin, Trees; Brink, Heleen van de

doi:10.1016/b978-0-08-033215-4.50058-3

Cited by 7 publications

(4 citation statements)

References 11 publications

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“…However, both ANA and LE-cell test are not specific for SLE. In contrast, antibodies to dsDNA are highly specific, and generally regarded as diagnostic ofSLE (4,32). We never found raised levels ofanti-dsDNA with the usual immunofluorescence test on Crithidia luciliae.…”

Section: Discussioncontrasting

confidence: 54%

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Acute Transverse Myelopathy as the Initial Manifestation of Probable Systemic Lupus Erythematosus in a Child

Linssen¹,

Fiselier²,

Gabreëls³

et al. 1988

Neuropediatrics

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Section: Discussioncontrasting

confidence: 54%

“…We never found raised levels ofanti-dsDNA with the usual immunofluorescence test on Crithidia luciliae. The presence of low avidity anti-dsDNA has been reported in association with an increased incidence of central nervous system involvement (32). In general, patients with Iow avidity had a more benign disease.…”

Section: Discussionmentioning

confidence: 97%

Acute Transverse Myelopathy as the Initial Manifestation of Probable Systemic Lupus Erythematosus in a Child

Linssen¹,

Fiselier²,

Gabreëls³

et al. 1988

Neuropediatrics

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“…Few crossreactions were shown with the phospholipids cardiolipin or phosphatidic acid, and those with chondroitin sulfate (21) were relatively rare. Cross-reactions with the polyanion dextran sulfate (22) by direct binding were infrequent, however, the same substance significantly inhibited binding to denatured DNA by an average of 36% of anti-denatured DNA mAbs. This apparent cross-reaction must be considered problematic because of the disparity between the direct binding and inhibition results.…”

Section: Methodsmentioning

confidence: 99%

Clonal analysis of the anti-DNA repertoire of murine B lymphocytes.

Conger¹,

Pike²,

Nossal³

1987

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

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The present studies characterize at the clonal level the repertoire of lipopolysaccharide-responsive murine B lymphocytes committed to the production of antibodies reactive with denatured DNA. This repertoire is vast in normal mice as 1-5% of total mitogen-induced antibody-forming cell clones secreted denatured DNA-reactive antibodies when the splenocyte donors were CBA (Ighi), BALB/c (Igha), C57BL/6 (Ighb), CBA nu/nu, and C57BL/6 nulnu athymic mice. The autoimmune NZB (Ighe) strain did not display elevated proportions of anti-denatured DNA antibody-forming cell precursors. Crossreactions shown by CBA anti-denatured DNA antibodies suggest that many antibodies might derive significant binding energy from interaction with the bases or similar hydrophobic moieties. Cross-reactions with other tested polynucleotides were frequent, but cross-reactions with phospholipids and phosphocholine were undetectable. Most anti-DNA antibodies bound preferentially or exclusively to single-stranded denatured DNA as compared to double-stranded native DNA. The frequency of anti-denatured DNA antibody-forming cell precursors among CBA peritoneal cells was not elevated. Fluorescence-activated cell sorter-selected Ly-1-positive NZB splenic B cells were not enriched, and Ly-1 negative B cells were not depleted of anti-DNA antibody-forming cell precursors. These results show that antibody-forming cell precursors specific for denatured DNA are not restricted to the Ly-1 positive B-cell subset.Elevated serum levels of anti-DNA antibodies are characteristic of human systemic lupus erythematosus and of autoimmune syndromes of certain inbred mouse strains, e.g., (NZB x NZW)F1, MRL-lpr/lpr, and BXSB (1, 2). The generation of monoclonal antibodies (mAbs) by hybridoma technology from B cells of such humans and mice has allowed detailed characterization of the anti-DNA antibodies. A remarkable range of cross-reactions with, for example, multiple polynucleotides, cardiolipin and other phospholipids, proteoglycans, haptens, and some intracellular proteins has been displayed (3-5). To understand whether a selective process is operative, it is necessary to compare the cross-reactivity patterns of monoclonal anti-DNA antibodies from normal and "autoimmune" donors. Other studies of the normal B-cell repertoire of mice (6-9) show a surprisingly high incidence of cells producing antibodies that can bind to self-antigens including DNA.Experiments of Hayakawa et al. (10) suggest that the subset of Ly-1-positive (Ly-1) B cells are of special importance in autoantibody production, including anti-DNA and anti-erythrocyte autoantibodies. The present experiments use in vitro clonal analysis for the identification of potentially anti-DNA antibody-forming cells (AFC) from normal, autoimmune, and congenitally athymic mouse strains and among cell populations enriched for Ly-1+ B cells.

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“…(Reaction patterns in the various anti-DNA assays of these monoclonals will be published later.) As reported previously, most anti-DNA-producing hybridomas, selected by use of an anti-DNA ELISA, make antibodies of low avidity toward DNA (31). When we tested the anti-DNA monoclonal antibodies in the anticardiolipin ELISA, 6 1o.OOo.…”

Section: Resultsmentioning

confidence: 99%

Is anticardiolipin activity a cross‐reaction of anti‐DNA or a separate entity?

Smeenk

Lucassen

Swaak

1987

Arthritis & Rheumatism

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Putative cross-reactions between anti-DNA and anticardiolipin activities were studied using sera of different patients and a panel of monoclonal antibodies to DNA. Sera were obtained from patients with systemic lupus erythematosus, from patients with syphilis, and from heroin addicts who showed a biologic false-positive result on the serologic test for syphilis. While the patients with syphilis and the heroin addicts had elevated levels of anticardiolipin antibodies in their circulation, no reactivity with DNA was observed in these sera. Sera from systemic lupus erythematosus patients often showed both anti-DNA and anticardiolipin activity. Although a correlation between anti-DNA and anticardiolipin titers was found, this did not always result from cross-reactivity of the same population of antibodies. In fact, we observed a relationship between cross-reactivity and antibody avidity. Anti-DNA of high avidity to DNA showed little cross-reactivity with cardiolipin. Anticardiolipin activity in such sera was based on the presence of specific anticardiolipin antibodies. Anti-DNA of low avidity was found to cross-react Submitted for publication August 12, 1986; accepted in revised form December 31, 1986. with cardiolipin. Among monoclonal antibodies to DNA, we found that cross-reactions with cardiolipin were rare: only 6 of 55 anti-DNA clones produced antibodies that also reacted with cardiolipin.

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Crossreactivity of Monoclonal Antibodies to DNA: Related to Avidity?

Cited by 7 publications

References 11 publications

Acute Transverse Myelopathy as the Initial Manifestation of Probable Systemic Lupus Erythematosus in a Child

Acute Transverse Myelopathy as the Initial Manifestation of Probable Systemic Lupus Erythematosus in a Child

Clonal analysis of the anti-DNA repertoire of murine B lymphocytes.

Is anticardiolipin activity a cross‐reaction of anti‐DNA or a separate entity?

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