The aim of this study was to examine whether circulating levels of the proinflammatory glycoprotein tenascin-C (TNC) are useful as an activity-specific or predictive biomarker in systemic lupus erythematosus (SLE).
Serum TNC levels were determined by enzyme-linked immunosorbent assay at inception visit in a prospective cohort of 59 SLE patients, and in 65 healthy controls (HC). SLE patients were followed for a mean of 11 months, disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) and British Isles Lupus Assessment Group disease activity index (BILAG-2004), clinical and laboratory data were recorded every 3-6 months, and changes in glucocorticoids (GC) and immunosuppressants (IS) were recorded serially. We examined cross-sectionally the relationships between serum concentrations of TNC and SLE status, SLEDAI-2 K scores, strata of disease activity, and levels of conventional biomarkers [anti-double-stranded DNA (dsDNA), anti-nucleosome antibodies, C3 and C4]. We also explored the utility of TNC levels for predicting disease flares, defined as (i) new/increased GC, (ii) new/increased GC or IS, and (iii) increase in SLEDAI by ≥3 or (iv) BILAG A or B flare.
There was no significant difference in the mean levels of TNC between the SLE patients and HC. However, in SLE patients with active disease (SLEDAI ≥6), the TNC levels were significantly higher than in the HC (p = 0.004) or in patients with no/low disease activity (p = 0.004). In SLE patients, TNC levels were significantly associated with positivity of anti-dsDNA (p = 0.03) and anti-nucleosome antibodies (p = 0.008). Flares defined by a need to escalate immunosuppressive therapy were captured more frequently and earlier than flares defined by standard activity indices. Higher baseline levels of serum TNC presented a significantly greater risk of flare (i) [hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.11-1.73] or (ii) (HR 1.25, 95% CI 1.02-1.52) but not of flares (iii) or (iv). The baseline serum TNC level was the single most important independent predictor of flare (i) compared with conventional biomarkers.
TNC is not disease-specific, but it seems to indicate the activity of SLE and may predict the need to escalate immunosuppressive therapy. TNC levels may thus serve as a useful activity-specific and predictive biomarker in SLE.