Murine monoclonal anti-DNA antibodies bind directly to glomerular antigens and form immune deposits.

Madaio, M. P.; Carlson, Jeanine A.; Cataldo, Jamyra Iglesias; Ucci, Angelo A.; Migliorini, Paola; Pankewycz, O.

doi:10.4049/jimmunol.138.9.2883

Cited by 225 publications

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“…Subsets of anti-DNA antibody, for example, are cross-reactive with other substances, including cardiolipin, heparan sulfate, vimentin, cell surfaces, and cell surface proteins (51)(52)(53)(54)(55)(56). Indeed, direct binding of anti-DNA antibodies to glomerular antigens has been demonstrated in vivo in a mouse model; this implies that no interaction with DNA is necessary and that only a particular subset of anti-DNA antibodies may be important (57). Neither of these caveats, however, reduces the importance of understanding the relationship of serum autoantibodies to the clinical expression of SLE.…”

Section: Discussionmentioning

confidence: 99%

A MODEL FOR DISEASE HETEROGENEITY IN SYSTEMIC LUPUS ERYTHEMATOSUS: Relationships Between Histocompatibility Antigens, Autoantibodies, and Lymphopenia or Renal Disease

Harley

Sestak²,

Willis³

et al. 1989

Arthritis & Rheumatology

163

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We composed a model from autoimmune serologic findings, HLA antigens, and clinical findings that explains, at least partially, the clinical heterogeneity of 40 patients with systemic lupus erythematosus (SLE). In these patients, anti–Ro (SS‐A) was related to the HLA–DQ1/DQ2 heterozygotes, anti–La (SS‐B) was related to HLA–B8 and HLA–DR3, and anti–nuclear RNP (Sm) was related to HLA–DR4. Lymphopenia was associated with anti–Ro (SS‐A) and, secondarily, with anti‐single‐stranded DNA. Renal disease in these SLE patients was inversely associated with anti–La (SS‐B) and was positively associated with anti–double‐stranded DNA. There were no associations between the HLA antigens and these clinical manifestations. The results support a model of disease expression in which individuals are nonspecifically potentiated for SLE. Their HLA antigen composition influences the production of particular autoantibodies that are related in complex ways to the different particular clinical findings of SLE manifested in individual patients.

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Section: Discussionmentioning

confidence: 99%

A MODEL FOR DISEASE HETEROGENEITY IN SYSTEMIC LUPUS ERYTHEMATOSUS: Relationships Between Histocompatibility Antigens, Autoantibodies, and Lymphopenia or Renal Disease

Harley

Sestak²,

Willis³

et al. 1989

Arthritis & Rheumatology

163

View full text Add to dashboard Cite

show abstract

Dual Specificity and the Formation of Stable Autoimmune Complexes

1997

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Since dual specificity at the antibody active-site level involves new principles relative to monospecific antigen-antibody interactions and may be a general property of autoantibodies, it was important to further characterize such antibodies. Four lupus derived autoantibodies were studied to understand parameters and mechanisms involved in the participation of dual-specific antibody molecules in the formation of highly stable immune complexes. Because the dual-specific binding properties of selected lupus-related murine autoantibodies had been previously described using a solid-phase polystyrene-based ELISA, a conformational sensitive membrane based assay (CSI) was used on a comparative basis to further characterize NZB/NZW F1 murine monoclonal anti-DNA autoantibodies BV 04-01 (anti-ssDNA), BV 16-19 (anti-ssDNA), BV 17-45 (anti-dsDNA), and BV 16-13 (anti-dsDNA). All four monoclonal autoantibodies exhibited anti-IgG binding in the solid-phase ELISA. However in the CSI assay, only anti-dsDNA monoclonal autoantibodies BV 17-45 and BV 16-13 demonstrated anti-IgG binding, while anti-ssDNA autoantibodies BV 04-01 and BV 16-19 did not. Upon subjection to time-dependent thermal denaturation, with and without thiol reduction at 100 degrees C in the CSI, the self-binding activities of BV 17-45 and BV 16-13 were abrogated demonstrating that the recognized IgG autoepitope(s) possessed conformational or discontinuous three-dimensional properties. The immunological implications of dual specificity are discussed on a structure-function basis and its correlation with formation of pathogenic immune complexes.

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Chronic parvovirus B19 infection induces the production of anti-virus antibodies with autoantigen binding properties

et al. 1998

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Human parvovirus B19 infection in adults shows some clinical features similar to those found in autoimmune connective tissue diseases. To better clarify the relationship between viral infection and autoimmunity, we have evaluated the ability of anti-parvovirus antibodies to specifically recognize autoantigens in ten patients with chronic symmetric arthritis resembling rheumatoid arthritis or with recurrent episodes of arthritis and cutaneous manifestations and persistence of specific IgM antibodies against B19 parvovirus. We synthetized a 24-amino acid immunodominant peptide corresponding to a part of the virus protein 1 and virus protein 2 overlapping region. The peptide has been used to test patients' sera at different time points with an enzyme-linked immunosorbent assay (ELISA) and to purify antivirus antibodies by affinity chromatography on a peptide-Sepharose column. Eluted immunoglobulins recognized the B19 peptide in both direct and competitive ELISA. Affinitypurified anti-parvovirus antibodies were then tested on a panel of autoantigens including human keratin, collagen type II, thyreoglobulin, single-strand (ss)DNA, cardiolipin and ribonucleoprotein antigen Sm. Eluted antibodies specifically recognized keratin, collagen type II, ssDNA and cardiolipin. Autoantibody activity was not detected in the immunoglobulin fraction after complete removal of anti-peptide antibodies and in antibodies eluted from normal donors. Epstein-Barr virus-transformed cell clones obtained from two subjects produced antibodies which simultaneously recognize the viral peptide and several autoantigens. To further confirm the role of the virus in inducing an autoantibody response, eight BALB/c mice were immunized with the viral peptide coupled to a carrier protein. Autoantibody activity against keratin, collagen II, cardiolipin and ssDNA was detected in six of the eight mice which developed a strong anti-virus response. Together, these data indicate that B19 parvovirus may be linked to the induction of an autoimmune response.

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Murine monoclonal anti-DNA antibodies bind directly to glomerular antigens and form immune deposits.

Cited by 225 publications

References 0 publications

A MODEL FOR DISEASE HETEROGENEITY IN SYSTEMIC LUPUS ERYTHEMATOSUS: Relationships Between Histocompatibility Antigens, Autoantibodies, and Lymphopenia or Renal Disease

A MODEL FOR DISEASE HETEROGENEITY IN SYSTEMIC LUPUS ERYTHEMATOSUS: Relationships Between Histocompatibility Antigens, Autoantibodies, and Lymphopenia or Renal Disease

Dual Specificity and the Formation of Stable Autoimmune Complexes

Chronic parvovirus B19 infection induces the production of anti-virus antibodies with autoantigen binding properties

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