Cited by 113Systemic Lupus Erythematosus ResearchSystemic Sclerosis and Related DiseasesVasculitis and related conditions

Anti-dsDNA antibodies and disease classification in antinuclear antibody positive patients: the role of analytical diversity

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Haugbro, K, Nossent, J C, Winkler, T, Figenschau, Y, Rekvig, O P·2004·Annals of the Rheumatic Diseases

Abstract

Background The presence of "anti-DNA antibodies in abnormal titres" is a well established criterion for SLE classification, but there is no agreement on the performance of this test.Objective To study the correlation between clinical findings and five different solid and solution phase anti-DNA antibody assays.Methods 158 consecutively collected ANA positive sera were studied in a double blind fashion. Anti-DNA antibodies were determined by different solid phase assays (ssDNA-, dsDNA- specific ELISA, EliA anti-dsDNA assay, Crithidia luciliae assay), and by an experimental solution phase anti-DNA assay using biotinylated pUC18 plasmid, human, calf thymus, and E coli DNA. Antibody affinity was determined by surface plasmon resonance. Clinical data were obtained independently of the laboratory analyses and later related to the anti-dsDNA findings.Results Anti-dsDNA antibodies were most frequently detected by ELISA, but were not specific for SLE as they were present in up to 30% of other disease groups. Those detected by the Crithidia luciliae assay were predictive for SLE, while antibodies binding in solution phase ELISA using the pUC18 correlated strongly with the Crithidia luciliae assay. Surface plasmon resonance analysis showed that antibody binding to pUC18 was not due to higher relative affinity for dsDNA in general, but apparently to specificity for that plasmid DNA. Serum samples from three patients with lupus nephritis were positive in both pUC18 solution phase and Crithidia luciliae assays.Conclusions Assay principle selection is decisive for the detection of clinically significant anti-DNA antibodies. Revision of the anti-DNA antibody criterion in the SLE classification may be needed.

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  • Despite low sensitivity (30% to 60%), CLIFT is useful in the diagnosis of SLE and to distinguish it from other diseases because of its high specificity.

    “Indeed, despite its low sensitivity, globally ranging from 30% to 60% [19,25,32,33], but owing to its high specificity, CLIFT is considered useful in the diagnosis of SLE and to distinguish it from other diseases [17,31,34].”

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  1. Berzofsky JA, Berkower IJ, Epstein SL. Antigen-antibody interactions and monoclonal antibodies. In: Paul WE, ed. Fundamental immunology, 4th ed. New York: Lippincott, Williams & Wilkins, 1998:75-110.
  2. Hirota Y, Ohyama T. Adjacent upstream superhelical writhe influences an Escherichia coli promoter as measured by in vivo strength and in vitro open complex formation. J Mol Biol 1995;254:566-78.
  3. Yoh K, Itoh K, Enomoto A, Hirayama A, Yamaguchi N, Kobayashi M, et al. Nrf2-deficient female mice develop lupus-like autoimmune nephritis. Kidney Int 2001;60:1343-53.
  4. Mohan C, Alas E, Morel L, Yang P, Wakeland EK. Genetic dissection of SLE pathogenesis. Sle1 on murine chromosome 1 leads to a selective loss of tolerance to H2A/H2B/DNA subnucleosomes. J Clin Invest 1998;101:1362-72.

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Authors
Haugbro, K., Nossent, J. C., Winkler, T., Figenschau, Y., & Rekvig, O. P.
Affiliations
  • UiT The Arctic University of Norway (NO)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • University Hospital of North Norway (NO)
Corresponding author
Rekvig, O P
Venue
Annals of the Rheumatic Diseases
Publisher
Elsevier BV
Published
2004-04
Volume
63
Issue
4
Pages
386-394
ISSN
0003-4967 (ISSN-L)
OpenAlex
W2109662991
Cited by
113
References
57
Citations by year
2026: 2 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 7 · 2018: 5 · 2017: 6 · 2016: 6 · 2015: 11 · 2014: 7 · 2013: 3 · 2012: 2
FWCI
4.65
Type
journal article
Language
en
Open access
Locations
  • Annals of the Rheumatic Diseases (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
Norges Forskningsråd
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
Keywords
anti-dsDNA antibodies, systemic lupus erythematosus, disease classification, antinuclear antibodies, antibody affinity, lupus nephritis, assay specificity, autoantibody detection
MeSH terms
Animals, Antibody Affinity, Antibodies, Antinuclear, Arthritis, Rheumatoid, Connective Tissue Diseases, Crithidia, DNA, Enzyme-Linked Immunosorbent Assay, Humans, Immunoglobulin G, Lupus Erythematosus, Systemic, Lupus Nephritis, Plasmids, Sensitivity and Specificity, Sjogren's Syndrome, Fluorescent Antibody Technique, Indirect, Surface Plasmon Resonance

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