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Biomarker studies
Original research
Associations of serum soluble Fas and Fas ligand (FasL) with outcomes in systemic lupus erythematosus
  1. Fabien B Vincent1,
  2. Rangi Kandane-Rathnayake1,
  3. Rachel Koelmeyer1,
  4. James Harris1,
  5. Alberta Y Hoi1,
  6. Fabienne Mackay2,3 and
  7. Eric F Morand1
  1. 1Centre for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
  2. 2Department of Immunology and Pathology, Monash University, Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), Melbourne, Victoria, Australia
  3. 3Department of Microbiology and Immunology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, Australia
  1. Correspondence to Professor Eric F Morand; eric.morand{at}monash.edu

Abstract

Objective Fas/Fas ligand (FasL) and B cell-activating factor (BAFF) signalling have pivotal roles in SLE pathogenesis. We investigated the clinical associations of serum concentrations of soluble Fas (sFas) and soluble FasL (sFasL) in SLE and their relationship with BAFF.

Methods Serum sFas and sFasL were quantified by multiplex assay, and BAFF by ELISA, in 118 patients with SLE and 17 healthy controls (HC). SLE disease activity and organ damage were assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics Damage Index.

Results sFas, sFasL and BAFF were detectable in all samples. Serum sFas and sFasL were significantly higher in SLE compared with HC. In univariable regression analyses, patients with active renal disease and those with flare had significantly higher levels of sFas compared with those without. High serum BAFF in patients with SLE was associated with increased sFas but not sFasL. The association between sFas and renal disease remained significant after adjusting for BAFF, but the association with flare attenuated. High sFas levels were associated with increased time-adjusted mean SLEDAI-2K, even after adjusting for BAFF, and with higher odds of flare over time. In contrast, high sFasL was associated with reduced organ damage over time. Serum sFasL/sFas ratio was negatively associated with active overall disease, flare and organ damage.

Conclusions Serum sFas is associated with active renal SLE, and active disease and flare over time, while sFasL/sFas ratio is negatively associated with disease activity and organ damage accrual. Treatments correcting abnormal levels of sFas/FasL may be worthy of evaluation in SLE.

  • autoimmunity
  • cytokines
  • systemic lupus erythematosus
  • lupus nephritis
  • autoimmune diseases
http://creativecommons.org/licenses/by-nc/4.0/

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, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/lupus-2019-000375

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    Footnotes

    • Contributors All authors contributed to experimental design, analysis and drafting of the paper. FV performed the ELISA and multiplex assays. Both FV and RK-R analysed the data. FV drafted the manuscript. All authors read and gave final approval of the version to be published.

    • Funding FV is a recipient of a Fellowship from Arthritis Australia. FM is a recipient of Fellowships from the NHMRC of Australia. EM was supported by the Kim Jolly Lupus Research Trust. The Monash Lupus database has received support from Arthritis and Osteoporosis Victoria, and unrestricted educational grants from GlaxoSmithKline, UCB, AstraZeneca and Eli Lilly Australia.

    • Competing interests EM has been a consultant to GSK and Eli Lilly. Other authors have no conflict of interest to declare.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Patient consent for publication Not required.

    • Ethics approval This study was approved by the Human Research Ethics Committee, Monash Health. The study was carried out in accordance with the National Statement on Ethical Conduct in Human Research (2007).

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

    • Data availability statement Data are available upon reasonable request. Reasonable requests to view the data set used in this manuscript can be made in writing to FV (fabien.vincent@monash.edu).