Anti-DNA antibodies and lupus nephritis: the complexity of crossreactivity

Brinkman, Kees; Termaat, R. M.; Berden, Jo H. M.; Smeenk, R. J. T.

doi:10.1016/0167-5699(90)90095-q

Cited by 97 publications

(46 citation statements)

References 24 publications

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“…anti-Ro/SS-A and anti-La/SS-B antibodies) [3]. The former are well known to be correlated with active nephritis in patients with SLE [4,5], the latter are not restricted to patients with SLE but are also found in sera of patients with Sjögren's syndrome [6,7].…”

Section: Introductionmentioning

confidence: 99%

Production of anti-Ro/SS-A and anti-La/SS-B Autoantibodies is Closely Coordinated in Systemic Lupus Erythematosus and Independent of anti-dsDNA Production

Meilof

Veldhoven

Swaak³

et al. 1997

Journal of Autoimmunity

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Autoimmune diseases such as Sjögren's Syndrome and systemic lupus erythematosus (SLE) are characterized by serum autoantibodies against protein components of small cytoplasmic ribonucleoproteins (scRNPs). The origin and regulation of these anti-Ro/SS-A and anti-La/SS-B antibodies is not well understood. Regular co-occurrence of these two autoantibodies in humans together with murine studies on antibody responses against scRNPs after immunization suggest a role for scRNPs as common antigen. We sought additional evidence for this hypothesis in a longitudinal serological study of patients with SLE. Quantitative measurement of the antibody responses against Ro/SS-A and La/SS-B proteins and for comparison to dsDNA in 852 serum samples was performed. These samples were collected from nine patients during an average observation period of more than 10 years. A significant and strong correlation between the two anti-scRNP responses emerged during 90% of follow-up. In contrast, correlation of anti-scRNP with anti-dsDNA responses was remarkably absent in the same patients. Our results confirm the unique relationship between anti-Ro/SS-A and anti-La/ SS-B responses and could thus be interpreted as support for a model wherein induction and perpetuation of autoantibody production is dependent on scRNPs containing both proteins as antigen.

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Section: Introductionmentioning

confidence: 99%

Production of anti-Ro/SS-A and anti-La/SS-B Autoantibodies is Closely Coordinated in Systemic Lupus Erythematosus and Independent of anti-dsDNA Production

Meilof

Veldhoven

Swaak³

et al. 1997

Journal of Autoimmunity

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“…Nephritogenie antibodies are predominantly ofthe IgG isotype [24,25]. Some argue that monospecific high avidity anti-dsDNA antibodies represent pathogenic antibodies [4], whereas others have found polyreactive antibodies eluted from the kidneys of SLE patients [25]. In addition, IgM antibodies have been found at sitesof tissue damage which bear anti-DNA antibody idiotypes [26].…”

Section: Discussionmentioning

confidence: 99%

“…Brinkmann et at. have challenged the notion of eross-reactivity being due to direct binding, and have proposed that DNA histone complexes mediate the polyreactivity [4].…”

Section: Discussionmentioning

confidence: 99%

“…The first was to examine antibodies present in sera from SLE patients, but it is difficult to determine whether cross-reactivity is due to the range of autoantibodies known to e.xist in SLE patients or to polyreactivity of individual autoantibodies. The produetion of MoAbs using hybridoma technology has allowed the analysis of individual antibodies [2.3] anti-DNA antibodies found in disease [4]. In particular, the MoAbs are often selected using an ELISA technique which detects low as well as high affinity antibodies and occasionally gives false positive results.…”

Section: Introductionmentioning

confidence: 99%

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Production and analysis of IgG monoclonal anti-DNA antibodies from systemic lupus erythematosus (SLE) patients

Ehrenstein¹,

Longhurst²,

Isenberg³

1993

Clinical and Experimental Immunology

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SUMMARYThis study compares recently devised tnethods for producing IgG anti-DNA MoAbs from patients with SLE and analyses the antibodies generated from one patient at different phases of disease. Lymphocytes from SLE patients were transformed with Epstein-Barr virus (EBV) and/or fused with a heteromyeloma cell line., CB-F7. Direct fusion with CB-F7 resulted in the highest proportion of lgG-secreting lines, whereas EBV transformation resulted in a high percentage of IgM-secreting lines. Using direet fusion, five IgM anti-DNA antibody-seereting hybridomas were generated using lymphoeytes from a patient with relatively inactive SLE. Six months later when the disease was active, only IgG anti-DNA antibodies were produced. The antigen-binding patterns of the MoAbs were analysed. Only one of the IgM anti-DNA antibodies reacted with dsDNA by ELISA and none by Crithidia immunofluorescenee, whereas two ofthe IgG antibodies reacted with dsDNA by ELISA and Crithidia but did not bind to ssDNA. Only the two IgG high affinity anti-dsDNA antibodies bound to histones, and this was enhanced by added DNA. whereas three IgM antibodies bound lo cardiolipin. This study supports the notion that MoAbs derived from a patient with SLE represent those found in the serum of SLE patients at different stages of disease aetivity. The binding to histones by the two IgG anti-dsDNA antibodies supports the recently expressed view that antibodies binding DNA/histone may be important in the pathogenesis of SLE.

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“…Several of them, including as many as 18 common Ids [ 13], may also be detectable in a lower proportion of further autoimmune conditions [14] and on normal IgG from healthy subjects [15]. However, because of the anionic sites of the human glomerular basement membrane [16], nephritogenic properties of anti-DNA molecules are usually paralleled by their complementary isoelectric cationic charge [17,18]. Thus, production of anti-Ids inhibiting the potentially harmful autoimmune repertoire may arise as a normal result of the natural regulatory network directed at autoantibodies secreted in normals by CD5^ B cells [19.20].…”

Section: Introductionmentioning

confidence: 99%

Pathogenic anti-DNA idiotype-reactive IgG in intravenous immunoglobulin preparations

Silvestris

Cafforio

Dammacco

1994

Clinical and Experimental Immunology

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SUMMARY This study was addressed to explore the reactivity of natural anti‐idiotypes from commercial lots of immunoglobulins to several idiotypes (Ids), usually expressed by anti‐DNA molecules in lupus nephritis. Eleven intravenous immunoglobulin (IVIG) preparations and nine (three polyvalent and six hyper‐immune) intramuscular IgG were Investigated for specific content of anti‐DNA, anti‐F(ab′)2 and antibodies reacting with several anti‐DNA IgG Ids. Two samples (nos 6 and 11) showed high reactivity with allogeneic F(ab′)2 and with F(ab′)2 of myeloma proteins bearing the anti‐DNA Id 31+ and the 8.12+. Since both 31 and 8.12 Id markers are known to characterize pathogenic anti‐DNA IgG in systemic lupus erythematosus (SLE), anti‐Id antibodies to these markers were obtained by absorbing the IVIG samples nos 6 and 11 to Sepharose columns coupled with pooled (ab′)2 fragments of 31+‐F4+‐8.12+‐myeloma proteins. Inhibition experiments showed that anti‐8.12 Id‐eluted IgG induced a selective suppression of the DNA‐reactive antibodies derived from patients with active lupus nephritis to their substrate, suggesting the involvement of 8.12+ molecules in the SLE glomerular damage. Since 8.12+ anti‐DNA are nephritogenic antibodies, the occurrence of anti‐8.12+ Id in commercial IVIG may be of potential therapeutic relevance in modulating the pathogenic SLE Id network. Previous variable results of IVIG treatment in SLE, such as resolution of proteinuria or worsening nephritis, could be related to variable enrichment of different lots of IVIG in suppressive anti‐pathogenic Id antibodies.

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Anti-DNA antibodies and lupus nephritis: the complexity of crossreactivity

Cited by 97 publications

References 24 publications

Production of anti-Ro/SS-A and anti-La/SS-B Autoantibodies is Closely Coordinated in Systemic Lupus Erythematosus and Independent of anti-dsDNA Production

Production of anti-Ro/SS-A and anti-La/SS-B Autoantibodies is Closely Coordinated in Systemic Lupus Erythematosus and Independent of anti-dsDNA Production

Production and analysis of IgG monoclonal anti-DNA antibodies from systemic lupus erythematosus (SLE) patients

Pathogenic anti-DNA idiotype-reactive IgG in intravenous immunoglobulin preparations

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