Article Text

other Versions

PDF
Lack of association between the interferon-alpha signature and longitudinal changes in disease activity in Systemic Lupus Erythematosus
  1. Carolina Landolt-Marticorena (w.kahr{at}utoronto.ca)
  1. University Health Network, Canada
    1. Gabriel Bonventi (gbonvent{at}uhnres.utoronto.ca)
    1. University Health Network, Canada
      1. Alla Lubovich (marconirl{at}hotmail.com)
      1. University Health Network, Canada
        1. Charmaine Ferguson (cferguso{at}uhnres.utoronto.ca)
        1. University Health Network, Canada
          1. Thulasi Unnitahn (thulasi.unnithan{at}uhnresearch.ca)
          1. University Health Network, Canada
            1. Jiandong Su (jsu{at}uhnresearch.ca)
            1. University Health Network, Canada
              1. Dafna D Gladman (dafna.gladman{at}utoronto.ca)
              1. University Health Network, Canada
                1. Murray Urowitz (m.urowitz{at}utoronto.ca)
                1. University Health Network, Canada
                  1. Paul R Fortin (pfortin{at}uhnresearch.ca)
                  1. University Health Network, Canada
                    1. Joan Wither (jwither{at}uhnres.utoronto.ca)
                    1. University Health Network, Canada

                      Abstract

                      Objective: To study the longitudinal expression of interferon (IFN)-inducible genes in systemic lupus erythematosus (SLE) and determine their suitability as disease biomarkers.

                      Methods: RNA was isolated from the peripheral blood of 94 SLE patients and 11 controls and reverse transcribed into cDNA. The expression levels of five IFN-responsive genes (LY6E, OAS1, IFIT1, ISG15 and MX1) were determined by quantitative PCR, normalized to GAPDH and summed to generate a global IFN score. Patients were followed longitudinally for a period of 3-12 months, and the association between disease activity, as measured by the SLEDAI-2K, and other clinical and laboratory variables examined.

                      Results: Expression of all five IFN-responsive genes was significantly elevated in SLE patients versus controls. Expression of LY6E, OAS1, IFIT1 and the global IFN score was associated with high disease activity. The global IFN score was also associated with active renal disease, a decreased C3, and the presence of anti- dsDNA or -RNA binding protein antibodies at a single point in time. However, there was a poor correlation between changes in this score and changes in disease activity, C3, or anti-dsDNA antibody levels in patients followed longitudinally. In most patients, the levels of IFN-induced gene expression remained relatively stable over 3-12 months despite marked changes in disease activity. Nevertheless, in patients with low/moderate disease activity, those with high IFN scores had a more recent history of sustained high disease activity.

                      Conclusion: The findings indicate that IFN-induced gene expression has limited clinical utility as a biomarker of acute changes in disease activity.

                      Statistics from Altmetric.com

                      Request permissions

                      If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.