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Anti-RNP antibodies are associated with the interferon gene signature but not decreased complement levels in SLE
  1. Erika L Hubbard1,2,
  2. David S Pisetsky3,4,
  3. Peter E Lipsky1,2
  1. 1 AMPEL BioSolutions LLC, Charlottesville, Virginia, USA
  2. 2 RILITE Foundation, Charlottesville, Virginia, USA
  3. 3 Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
  4. 4 Rheumatology, Durham VA Medical Center, Durham, North Carolina, USA
  1. Correspondence to Dr Peter E Lipsky, RILITE Foundation, Charlottesville, VA 22902, USA; peterlipsky{at}comcast.net

Abstract

Objectives The goals of these studies were to elucidate the inter-relationships of specific anti-nuclear antibody (ANA), complement, and the interferon gene signature (IGS) in the pathogenesis of systemic lupus erythematosus (SLE).

Methods Data from the Illuminate trials were analysed for antibodies to dsDNA as well as RNA-binding proteins (RBP), levels of C3, C4 and various IGS. Statistical hypothesis testing, linear regression analyses and classification and regression trees analysis were employed to assess relationships between the laboratory features of SLE.

Results Inter-relationships of ANAs, complement and the IGS differed between patients of African Ancestry (AA) and European Ancestry (EA); anti-RNP and multiple autoantibodies were more common in AA patients and, although both related to the presence of the IGS, relationships between autoantibodies and complement differed. Whereas, anti-dsDNA had an inverse relationship to C3 and C4, levels of anti-RNP were not related to these markers. The IGS was only correlated with anti-dsDNA in EA SLE and complement was more correlated to the IGS in AA SLE. Finally, autoantibodies occurred in the presence and absence of the IGS, whereas the IGS was infrequent in anti-dsDNA/anti-RBP-negative SLE patients.

Conclusion There is a complex relationship between autoantibodies and the IGS, with anti-RNP associated in AA and both anti-dsDNA and RNP associated in EA. Moreover, there was a difference in the relationship between anti-dsDNA, but not anti-RBP, with complement levels. The lack of a relationship of anti-RNP with C3 and C4 suggests that anti-RNP immune complexes (ICs) may drive the IGS without complement fixation, whereas anti-dsDNA ICs involve complement consumption.

  • autoantibodies
  • lupus erythematosus
  • systemic
  • cytokines

Data availability statement

Data are available in a public, open access repository. Data are available in a public, open access repository. Data were downloaded from Gene Expression Omnibus (GEO) under accession GSE88884.

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Data availability statement

Data are available in a public, open access repository. Data are available in a public, open access repository. Data were downloaded from Gene Expression Omnibus (GEO) under accession GSE88884.

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors ELH analysed the data and wrote the manuscript. DSP and PEL contributed to the conception, design and oversaw conduct of the research, edited the manuscript and made the decision to publish; thus, DSP and PEL were the guarantors.

  • Funding This work was supported by a grant from the RILITE Foundation.

  • Competing interests The authors have no competing interests to disclose. ELH and PEL are salaried employees of AMPEL BioSolutions, LLC.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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