The binding of lupus-derived autoantibodies to the C-terminal peptide (83-119) of the major SmD1 autoantigen can be mediated by double-stranded DNA and nucleosomes

Dieker, Jürgen; Bavel, C.C.A.W. van; Riemekasten, Gabriela; Berden, Jo H. M.; Vlag, Johan van der

doi:10.1136/ard.2005.043992

Cited by 9 publications

(5 citation statements)

References 15 publications

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“…Riemkasten and colleagues reported anti-SmD reactivity in 70.0% of SLE patients and in only 8.3% of controls using a SmD1 synthetic peptide [ 15 ]. This peptide, but not the full-length protein, has been shown to bind dsDNA contained in blocking reagents, which may result in the detection of anti-dsDNA antibodies in the SmD peptide ELISA [ 32 ]. In the present study we confirmed the dsDNA binding property of the SmD1 peptide.…”

Section: Discussionmentioning

confidence: 99%

Effect of dsDNA binding to SmD-derived peptides on clinical accuracy in the diagnosis of systemic lupus erythematosus

et al. 2007

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Systemic lupus erythematosus is characterized by antibodies to a variety of intracellular self-antigens, such as dsDNA and Sm, and these serve as hallmarks in the diagnosis of systemic autoimmune diseases. Several studies have shown that SmD1 and SmD3 synthetic peptides represent highly functional antigens for autoantibody detection and thus for diagnostic applications. The present study analysed the technical and clinical accuracy of an anti-SmD1 (amino acids 83-119) and an anti-SmD3 (amino acids 108-122) ELISA for the detection of anti-Sm antibodies. Depending on the cut-off value of the SmD1 ELISA, we found a high degree of concordance between the two tests. At an optimized cut-off value of 100 units for SmD1 we found the same clinical sensitivity (12.5%) and specificity (100%) in a group of systemic lupus erythematosus patients (n = 48) and in controls (n = 99). The concordance at this cut-off value was 100% (P < 0.0001; χ 2 = 127.61). Using a second panel of sera (n = 65) preselected based on positive anti-Sm results, we confirmed the high degree of concordance between the two assays. Using dsDNA-coated ELISA plates and biotinylated peptides we confirmed the high dsDNA binding properties for SmD1, which were significantly higher than the SmD3-derived peptide. However, no cross-linking of antidsDNA antibodies to SmD1 was observed after adding increasing amounts of dsDNA to anti-dsDNA positive, antiSmD1 negative serum. We therefore conclude that the reported difference in the sensitivity is related to the different cut-off levels and not to the detection of anti-dsDNA antibodies bridged via dsDNA to the SmD1 peptide. Moreover, we found that a subpopulation of anti-Sm antibodies cross-reacted with SmD1 and SmD3. Taken together, the data indicate that both SmD peptide ELISAs represent accurate assays and may be used as important standards for the detection of anti-Sm antibodies.

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Section: Discussionmentioning

confidence: 99%

Effect of dsDNA binding to SmD-derived peptides on clinical accuracy in the diagnosis of systemic lupus erythematosus

et al. 2007

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“…75 Another SmD1‐derived epitope comprising residues 83–119 has been identified and is recognized by a large number of SLE sera (see Table 3). 72 However, the high prevalence of reactivity in this setting is possibly a result of the DNA‐binding capacity of SmD1 83–119, which also binds anti‐dsDNA aAbs present in the sera of SLE patients 122,123 …”

Section: Clinically Relevant Epitopes (Peptides)mentioning

confidence: 99%

Epitope specificity and significance in systemic autoimmune diseases

Mähler

Fritzler

2010

Annals of the New York Academy of Sciences

112

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Autoimmune diseases are characterized by self-reactive immune processes mediated by B and T cells. These disorders exhibit a spectrum of clinical features that range from local or organ specific to systemic diseases. Although a variety of putative mechanisms that trigger the loss of tolerance and thus the genesis of autoimmunity have been identified, for the most part the precise mechanisms remain elusive. Nevertheless, it is widely appreciated that autoantibodies are useful both in the diagnosis of autoimmune disorders and as molecular biological tools to study cellular processes in which the target antigens are involved. Several methods and technologies, including protein fragments, synthetic peptides, phage display, or structural analyses have been developed for the characterization of the specificity of the autoimmune reactions. The present review provides an overview of the autoantibody epitopes in systemic autoimmune diseases as they relate to the clinical relevance and applications of certain autoepitopes and the technologies that are used to classify and identify them.

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“…Among these models, (NZB × NZW) F1 mice are considered to be most representative of SLE in humans (8,21,38). Female (NZB × NZW) F1 mice are characterized by the production of antinuclear antibodies, including anti-dsDNA antibodies, and the development of severe immune complex-mediated glomerulonephritis (17,42). According to data from the Jackson laboratory, these female mice have an average life span of only 245 days (35 weeks) owing to the development of renal failure.…”

Section: Introductionmentioning

confidence: 99%

Comparative Efficacies of Long-Term Serial Transplantation of Syngeneic, Allogeneic, Xenogeneic, or CTLA4Ig-Overproducing Xenogeneic Adipose Tissue-Derived Mesenchymal Stem Cells on Murine Systemic Lupus Erythematosus

et al. 2016

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Allogeneic and xenogeneic transplantation are suitable alternatives for treating patients with stem cell defects and autoimmune diseases. The purpose of this study was to compare the effects of long-term serial transplantation of adipose tissue-derived mesenchymal stem cells (ASCs) from (NZB × NZW) F1 mice (syngeneic), BALB/c mice (allogeneic), or humans (xenogeneic) on systemic lupus erythematosus (SLE). The effects of transplanting human ASCs overproducing CTLA4Ig (CTLA4Ig-hASC) were also compared. Animals were divided into five experimental groups, according to the transplanted cell type. Approximately 500,000 ASCs were administered intravenously every 2 weeks from 6 to 60 weeks of age to all mice except for the control mice, which received saline. The human ASC groups (hASC and CTLA4Ig-hASC) showed a 13-week increase in average life spans and increased survival rates and decreased blood urea nitrogen, proteinuria, and glomerular IgG deposition. The allogeneic group also showed higher survival rates compared to those of the control, up to 40, 41, 42, 43, 44, 45, 52, and 53 weeks of age. Syngeneic ASC transplantation did not accelerate the mortality of the mice. The mean life span of both the syngeneic and allogeneic groups was prolonged for 6-7 weeks. Both human ASC groups displayed increased serum interleukin-10 and interleukin-4 levels, whereas both mouse ASC groups displayed significantly increased GM-CSF and interferon-γ levels in the serum. The strongest humoral immune response was induced by xenogeneic transplantation, followed by allogeneic, CTLA4Ig-xenogeneic, and syngeneic transplantations. Long-term serial transplantation of the ASCs from various sources displayed different patterns of cytokine expression and humoral responses, but all of them increased life spans in an SLE mouse model.

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The binding of lupus-derived autoantibodies to the C-terminal peptide (83-119) of the major SmD1 autoantigen can be mediated by double-stranded DNA and nucleosomes

Abstract: The SmD1(83-119) peptide is able to bind dsDNA and nucleosomes, and dsDNA or nucleosomes in applied reagents lead to an apparent reactivity of anti-dsDNA, anti-histone or nucleosome-specific antibodies with the SmD1(83-119) peptide in ELISA.

Cited by 9 publications

References 15 publications

Effect of dsDNA binding to SmD-derived peptides on clinical accuracy in the diagnosis of systemic lupus erythematosus

Effect of dsDNA binding to SmD-derived peptides on clinical accuracy in the diagnosis of systemic lupus erythematosus

Epitope specificity and significance in systemic autoimmune diseases

Comparative Efficacies of Long-Term Serial Transplantation of Syngeneic, Allogeneic, Xenogeneic, or CTLA4Ig-Overproducing Xenogeneic Adipose Tissue-Derived Mesenchymal Stem Cells on Murine Systemic Lupus Erythematosus

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