Autoantibodies in SLE but not in scleroderma react with protein-stripped nucleosomes

Suer, Waltraud; Dähnrich, Cornelia; Schlumberger, Wolfgang; Stöcker, W.

doi:10.1016/j.jaut.2004.02.002

Cited by 35 publications

(22 citation statements)

References 19 publications

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“…Having shown enhancement for purified DNA, we next tested nucleosomes as the antigen. As shown in Fig 2 and S2 Table, a PLL pre-coat augmented binding to nucleosomes; antibodies to nucleosomes commonly co-exist with antibodies to DNA and represent overlapping specificities, although, depending on the preparation, nucleosomes may contain other antigens [38]. In the context of these experiments, these findings suggest that nucleosomes can bind PLL to increase the concentration of antigen on the plate.…”

Section: Resultsmentioning

confidence: 89%

The Use of Poly-L-Lysine as a Capture Agent to Enhance the Detection of Antinuclear Antibodies by ELISA

et al. 2016

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Antibodies to nuclear antigens (antinuclear antibodies or ANAs) are the serological hallmark of systemic lupus erythematosus (SLE). These antibodies bind diverse nuclear antigens that include DNA, histones and non-histone proteins as well as complexes of proteins with DNA and RNA. Because of the frequency of ANA expression in SLE, testing is an important component of clinical evaluation as well as determination of eligibility for clinical trials or utilization of certain therapies. Immunofluorescence assays have been commonly used for this purpose although this approach can be limited by issues of throughput, variability and difficulty in determining positivity. ELISA and multiplex assays are also useful approaches although these assays may give an incomplete picture of antibodies present. To develop a sensitive and quantitative ANA assay, we have explored an ELISA platform in which plates are pre-coated with a positively charged nucleic acid binding polymer (NABP) to increase adherence of antigens containing DNA or RNA. As a source of antigens, we have used supernatants of Jurkat cells undergoing apoptosis in vitro. As results presented show, a poly-L-lysine (PLL) pre-coat significantly enhances detection of antibodies to DNA as well as antigens such as histones, SSA, SSB and RNP. Comparison of the ELISA assay with the PLL pre-coat with a multiplex assay using the BioPlex® 2200 system indicated good agreement in results for a panel of lupus sera. Together, these studies indicate that a pre-coat with a positively charged polymer can increase the sensitivity of an ANA ELISA using as antigens molecules released from dead and dying cells. This assay platform may facilitate ANA testing by providing an ensemble of antigens more similar in composition and structure with antigens present in vivo, with a NABP promoting adherence via charge-charge interactions.

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Section: Resultsmentioning

confidence: 89%

The Use of Poly-L-Lysine as a Capture Agent to Enhance the Detection of Antinuclear Antibodies by ELISA

et al. 2016

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“…10 Second-generation anti-nucleosome ELISAs utilized chromatin chemically stripped of H1 and other loosely bound proteins like Scl-70 and, therefore, achieved superior diagnostic performance in SLE. 17 Interestingly, ELISAs using the strong adhesive property of nucleosomes (instead of commonly used linkers like methylated albumin, protamine sulfate or poly-L-lysine) to attach dsDNA to the plate, showed even higher diagnostic performance in SLE, and outperformed even the Farr assay. 14 …”

Section: Diagnostic Utilitymentioning

confidence: 99%

Autoantibodies, complement and type I interferon as biomarkers for personalized medicine in SLE

Biesen

Rose

Hoyer

et al. 2016

Lupus

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Systemic lupus erythematosus (SLE) can be a mysterious disease, presenting with extremely divergent clinical phenotypes. Already, biomarkers are very helpful tools for diagnosis, assessment and monitoring of disease activity, differential diagnosis of clinical manifestations, prediction of the disease course and stratified therapy, and they hold the key to personalized medicine in SLE. We summarize the clinical information that can only be supplied by autoantibodies, complement components and interferon biomarkers in this diverse disease.

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“…The prevalence of anti-nucleosomal antibodies (ANuA) in SLE sera is reported to be approximately 60% [60][61][62][63][64][65][66][67][68][69][70][71]. Several studies analysed the diagnostic accuracy and clinical relevance of ANuA using different antigen sources and detection methods, and their relationship to anti-dsDNA antibodies [60][61][62][63][64][65][66][67][68][69][70][71].…”

Section: Anti-nucleosomes (Chromatin)mentioning

confidence: 99%

“…Several studies analysed the diagnostic accuracy and clinical relevance of ANuA using different antigen sources and detection methods, and their relationship to anti-dsDNA antibodies [60][61][62][63][64][65][66][67][68][69][70][71]. Some studies reported that ANuA assays had a higher sensitivity than anti-dsDNA for SLE while other studies did not confirm this finding [61,69].…”

Section: Anti-nucleosomes (Chromatin)mentioning

confidence: 99%

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Challenges and Controversies in Autoantibodies Associated with Systemic Rheumatic Diseases

Mähler¹,

Raijmakers²,

Fritzler

2007

CRR

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Since the first identification of self-reactive antibodies in systemic lupus erythematosus and other systemic autoimmune rheumatic diseases, many autoantibodies have been identified as useful probes in molecular and cell biology and as diagnostic and prognostic biomarkers in clinical immunology. Among the autoantigens, double-stranded desoxoribonucleic acid (dsDNA), the Smith antigen (Sm), ribonucleoproteins (RNP), Scl-70 (topoisomerase I), proliferating cell nuclear antigen (PCNA), and others were described as serologic hallmarks in the diagnosis of systemic autoimmune rheumatic diseases. Despite these advances in identifying autoantibody markers, a number of challenges and controversies persist concerning their origin, clinical usefulness and relevance. These include the association between anti-ribosomal P antibodies and clinical features in systemic lupus erythematosus, the disease specificity of several autoantibodies (i.e. chromatin, Jo-1, alpha-fodrin, topo I and CENP), the relationship between the SS-A/Ro52 and SS-A/Ro60 autoantibody system(s) and the detection of anti-RNP/Sm and anti-fibrillarin antibodies.

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Autoantibodies in SLE but not in scleroderma react with protein-stripped nucleosomes

Cited by 35 publications

References 19 publications

The Use of Poly-L-Lysine as a Capture Agent to Enhance the Detection of Antinuclear Antibodies by ELISA

The Use of Poly-L-Lysine as a Capture Agent to Enhance the Detection of Antinuclear Antibodies by ELISA

Autoantibodies, complement and type I interferon as biomarkers for personalized medicine in SLE

Challenges and Controversies in Autoantibodies Associated with Systemic Rheumatic Diseases

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