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Two major autoantibody clusters in systemic lupus erythematosus

PLoS ONE, ISSN: 1932-6203, Vol: 7, Issue: 2, Page: e32001
2012
  • 92
    Citations
  • 0
    Usage
  • 114
    Captures
  • 0
    Mentions
  • 5
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    92
  • Captures
    114
  • Social Media
    5
    • Shares, Likes & Comments
      5
      • Facebook
        5

Article Description

Systemic lupus erythematosus is a chronic autoimmune disease of complex clinical presentation and etiology and is likely influenced by numerous genetic and environmental factors. While a large number of susceptibility genes have been identified, the production of antibodies against a distinct subset of nuclear proteins remains a primary distinguishing characteristic in disease diagnosis. However, the utility of autoantibody biomarkers for disease sub-classification and grouping remains elusive, in part, because of the difficulty in large scale profiling using a uniform, quantitative platform. In the present study serological profiles of several known SLE antigens, including Sm-D3, RNP-A, RNP-70k, Ro52, Ro60, and La, as well as other cytokine and neuronal antigens were obtained using the luciferase immunoprecipitation systems (LIPS) approach. The resulting autoantibody profiles revealed that 88% of a pilot cohort and 98% of a second independent cohort segregated into one of two distinct clusters defined by autoantibodies against Sm/anti-RNP or Ro/La autoantigens, proteins often involved in RNA binding activities. The Sm/RNP cluster was associated with a higher prevalence of serositis in comparison to the Ro/La cluster (P = 0.0022). However, from the available clinical information, no other clinical characteristics were associated with either cluster. In contrast, evaluation of autoantibodies on an individual basis revealed an association between anti-Sm (P = 0.006), RNP-A (P = 0.018) and RNP-70k (P = 0.010) autoantibodies and mucocutaneous symptoms and between anti-RNP-70k and musculoskeletal manifestations (P = 0.059). Serologically active, but clinically quiescent disease also had a higher prevalence of anti-IFN-α autoantibodies. Based on our findings that most SLE patients belong to either a Sm/RNP or Ro/La autoantigen cluster, these results suggest the possibility that alterations in RNA-RNA-binding protein interactions may play a critical role in triggering and/or the pathogenesis of SLE.

Bibliographic Details

http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84857420334&origin=inward; http://dx.doi.org/10.1371/journal.pone.0032001; http://www.ncbi.nlm.nih.gov/pubmed/22363785; https://dx.plos.org/10.1371/journal.pone.0032001; https://dx.plos.org/10.1371/journal.pone.0032001.g002; http://dx.doi.org/10.1371/journal.pone.0032001.g002; https://dx.plos.org/10.1371/journal.pone.0032001.t006; http://dx.doi.org/10.1371/journal.pone.0032001.t006; https://dx.plos.org/10.1371/journal.pone.0032001.t007; http://dx.doi.org/10.1371/journal.pone.0032001.t007; https://dx.plos.org/10.1371/journal.pone.0032001.t003; http://dx.doi.org/10.1371/journal.pone.0032001.t003; https://dx.plos.org/10.1371/journal.pone.0032001.g003; http://dx.doi.org/10.1371/journal.pone.0032001.g003; https://dx.plos.org/10.1371/journal.pone.0032001.t002; http://dx.doi.org/10.1371/journal.pone.0032001.t002; https://dx.plos.org/10.1371/journal.pone.0032001.t005; http://dx.doi.org/10.1371/journal.pone.0032001.t005; https://dx.plos.org/10.1371/journal.pone.0032001.t004; http://dx.doi.org/10.1371/journal.pone.0032001.t004; https://dx.plos.org/10.1371/journal.pone.0032001.t001; http://dx.doi.org/10.1371/journal.pone.0032001.t001; https://dx.plos.org/10.1371/journal.pone.0032001.g001; http://dx.doi.org/10.1371/journal.pone.0032001.g001; https://dx.doi.org/10.1371/journal.pone.0032001; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0032001; https://dx.doi.org/10.1371/journal.pone.0032001.t007; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0032001.t007; https://dx.doi.org/10.1371/journal.pone.0032001.g003; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0032001.g003; https://dx.doi.org/10.1371/journal.pone.0032001.t005; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0032001.t005; https://dx.doi.org/10.1371/journal.pone.0032001.g002; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0032001.g002; https://dx.doi.org/10.1371/journal.pone.0032001.t004; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0032001.t004; https://dx.doi.org/10.1371/journal.pone.0032001.t006; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0032001.t006; https://dx.doi.org/10.1371/journal.pone.0032001.t002; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0032001.t002; https://dx.doi.org/10.1371/journal.pone.0032001.t001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0032001.t001; https://dx.doi.org/10.1371/journal.pone.0032001.t003; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0032001.t003; https://dx.doi.org/10.1371/journal.pone.0032001.g001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0032001.g001; http://dx.plos.org/10.1371/journal.pone.0032001.g002; http://dx.plos.org/10.1371/journal.pone.0032001.t004; http://dx.plos.org/10.1371/journal.pone.0032001.t007; http://dx.plos.org/10.1371/journal.pone.0032001.t002; https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0032001&type=printable; http://dx.plos.org/10.1371/journal.pone.0032001.t001; http://dx.plos.org/10.1371/journal.pone.0032001.g001; http://dx.plos.org/10.1371/journal.pone.0032001; http://dx.plos.org/10.1371/journal.pone.0032001.t003; http://dx.plos.org/10.1371/journal.pone.0032001.t006; http://dx.plos.org/10.1371/journal.pone.0032001.g003; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0032001; http://dx.plos.org/10.1371/journal.pone.0032001.t005; http://www.plosone.org/article/metrics/info:doi/10.1371/journal.pone.0032001; http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0032001&type=printable; http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0032001; http://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0032001

Kathryn H. Ching; Peter D. Burbelo; Christopher Tipton; Chungwen Wei; Michelle Petri; Ignacio Sanz; Michael J. Iadarola; Michael P. Bachmann

Public Library of Science (PLoS)

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Multidisciplinary

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