title: Serum tenascin-C discriminates patients with active SLE from inactive patients and healthy controls and predicts the need to escalate immunosuppressive therapy: a cohort study.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Na Slupi 4, Praha 2, 12850, Prague, Czech Republic. zavada@revma.cz.
authors.forename: Jakub
authors.initials: J
authors.lastname: Závada
authors.affiliation: Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic. uher@iba.muni.cz.
authors.forename: Michal
authors.initials: M
authors.lastname: Uher
authors.affiliation: Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Na Slupi 4, Praha 2, 12850, Prague, Czech Republic. svobodova.r@revma.cz.
authors.forename: Radka
authors.initials: R
authors.lastname: Svobodová
authors.affiliation: Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Na Slupi 4, Praha 2, 12850, Prague, Czech Republic. olejarova@revma.cz.
authors.forename: Marta
authors.initials: M
authors.lastname: Olejárová
authors.affiliation: Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Na Slupi 4, Praha 2, 12850, Prague, Czech Republic. husakova@revma.cz.
authors.forename: Markéta
authors.initials: M
authors.lastname: Hušáková
authors.affiliation: Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Na Slupi 4, Praha 2, 12850, Prague, Czech Republic. ciferska@revma.cz.
authors.forename: Hana
authors.initials: H
authors.lastname: Ciferská
authors.affiliation: Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Na Slupi 4, Praha 2, 12850, Prague, Czech Republic. hulejova@revma.cz.
authors.forename: Hana
authors.initials: H
authors.lastname: Hulejová
authors.affiliation: Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Na Slupi 4, Praha 2, 12850, Prague, Czech Republic. tomcik@revma.cz.
authors.forename: Michal
authors.initials: M
authors.lastname: Tomčík
authors.affiliation: Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Na Slupi 4, Praha 2, 12850, Prague, Czech Republic. senolt@revma.cz.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Šenolt
authors.affiliation: Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Na Slupi 4, Praha 2, 12850, Prague, Czech Republic. vencovsky@revma.cz.
authors.forename: Jiří
authors.initials: J
authors.lastname: Vencovský
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D019063:Tenascin / Q000097:blood*
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D019063:Tenascin