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.
- lupus erythematosus
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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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.
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