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Distinct Autoantibody Profiles in Systemic Lupus Erythematosus Patients are Selectively Associated with TLR7 and TLR9 Upregulation

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Abstract

Purpose

Systemic lupus erythematosus (SLE) patients have a wide array of autoantibodies against nuclear antigens. The two predominant classes of these autoantibodies are directed either against dsDNA or RNA-associated antigens (extractable nuclear antigens; ENA). Nucleic-acid sensing Toll-like receptors (TLRs) that recognize dsDNA and RNA, have been well implicated in some murine models of SLE. We took up this study to identify if unique TLR expression patterns are associated with distinct autoantibody profiles in SLE.

Methods

We segregated the patients into three subsets distinguished on the basis of autoantibody response either against dsDNA or ENA or both. We determined the mRNA expression of TLR3, 7, 8, and 9 by real-time reverse-transcription PCR in peripheral blood leucocytes (PBLs) of the SLE patients of all three subsets. TLR7 and 9 protein expression was determined by western blotting in PBLs and by flow cytometry on B-cells and monocytes. The serum interferon-alpha (IFN-α) and anti-dsDNA/-ENA autoantibodies were detected using enzyme-linked immunosorbant assay.

Results

We report differential and unique TLR expression patterns associated with different autoantibody profiles. The presence of anti-ENA and anti-dsDNA autoantibodies in SLE patients was associated with elevated levels of TLR7 and TLR9 respectively. The TLR9 mRNA expression was further augmented in SLE patients with Glomerulonephritis. Interestingly, anti-dsDNA+ ENA+ patients displayed higher serum IFN-α and interferon regulatory factor 7 mRNA expression than patients with either anti-dsDNA or anti-ENA autoantibodies alone.

Conclusion

Characteristic TLRs expression profile associated with distinct autoantibody repertoire is suggestive of differential immuno-regulatory pathways operative in different subsets of SLE patients.

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Acknowledgements

This study was supported by a grant (BT/PR12772/BRB/10/722/2009) from the Department of Biotechnology, New Delhi, India. SKC is supported by senior research fellowship from Indian Council of Medical Research, New Delhi. The funding source had no involvement in study design, collection, analysis and interpretation of data, in the writing of the report as well as in the decision to submit the paper for publication. The authors would like to thank Dr Rose G. Mage, Laboratory of Immunology, National Institute of Health, Bethesda, USA for her valuable suggestions about the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India

    Sudhir Kumar Chauhan, Vikas Vikram Singh, Richa Rai & Geeta Rai

  2. Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

    Madhukar Rai

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  1. Sudhir Kumar Chauhan
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Correspondence to Geeta Rai.

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Chauhan, S.K., Singh, V.V., Rai, R. et al. Distinct Autoantibody Profiles in Systemic Lupus Erythematosus Patients are Selectively Associated with TLR7 and TLR9 Upregulation. J Clin Immunol 33, 954–964 (2013). https://doi.org/10.1007/s10875-013-9887-0

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  • DOI: https://doi.org/10.1007/s10875-013-9887-0

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