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Brief communication
Associations between type I interferon and antiphospholipid antibody status differ between ancestral backgrounds
  1. Taro Iwamoto1,
  2. Jessica Dorschner2,
  3. Meenakshi Jolly3,
  4. Xiangyang Huang4 and
  5. Timothy B Niewold1
  1. 1Department of Medicine and Pathology, Colton Center for Autoimmunity, New York University School of Medicine, New York, USA
  2. 2Department of Immunology, Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA
  3. 3Division of Rheumatology, Rush University Medical Center, Chicago, Illinois, USA
  4. 4Department of Rheumatology, The Second Xiangya Hosptal, Central South University, Changsha, Hunan 410011, China
  1. Correspondence to Dr Xiangyang Huang, Department of Rheumatology,The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China, ; yangyang1029{at}aliyun.com and Dr Timothy B Niewold; Timothy.Niewold{at}nyumc.org

Abstract

Objective The type I interferon pathway is activated in many patients with systemic lupus erythematosus (SLE), and anti-double-stranded DNA (dsDNA) and anti-RNA binding protein autoantibodies are correlated with high interferon-α (IFNα) activity. We studied whether antiphospholipid (APL) antibodies, which should not stimulate Toll-like receptors, are also associated with high levels of IFNα activity.

Methods Serum IFNα activity was measured in patients with SLE using the WISH cell bioassay. IgG APL, anti-RBP and anti-dsDNA antibodies were measured in the clinical laboratory, and standard clinical cut-offs were used to define the positive results.

Results High IFNα activity was associated with anti-RBP and anti-dsDNA antibodies in all three ancestral backgrounds. Strikingly, African-American subjects with a positive APL antibody test had higher IFNα activity than those without IgG APL antibodies. This was not shared with other ancestral backgrounds. This finding was independent of other autoantibody profiles, and clinical features did not differ between IgG APL antibody positive versus negative African-American patients.

Conclusion The difference in association between IFNα activity and IgG APL status between ancestral backgrounds supports differences in molecular pathogenesis. This may suggest B cell hyperactivity in the setting of type I IFN in African-Americans and could suggest ways to individualise therapy.

  • systemic lupus erythematosus
  • cytokines
  • antiphospholipid antibodies

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/lupus-2017-000246

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    Footnotes

    • Contributors TI and TBN designed the study, analysed the data and wrote the manuscript. JD performed the experiments, analysed the data and contributed to the manuscript. MJ and XYH generated and analysed the data and contributed to the manuscript.

    • Funding NIH grants (AR060861, AR057781, AR065964, AI071651), the Mayo Clinic Foundation, the Lupus Research Alliance and the Colton Center for Autoimmunity to TBN. National Natural Science Fund of China (No. 81072477)

    • Competing interests TBN has received research grants from Janssen and EMD Serono which are unrelated to the current study.

    • Patient consent Obtained

    • Ethics approval Institutional Review Board at the respective institutions.

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

    • Data sharing statement Interferon data from this paper could be made available upon request for a meritorious and non-overlapping project proposed with appropriate ethics approval.