PMID- 26608564 OWN - NLM STAT- MEDLINE DCOM- 20160907 LR - 20181113 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 17 DP - 2015 Nov 25 TI - 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. PG - 341 LID - 10.1186/s13075-015-0862-4 [doi] LID - 341 AB - INTRODUCTION: 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. FAU - Zavada, Jakub AU - Zavada J AD - 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. FAU - Uher, Michal AU - Uher M AD - Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic. uher@iba.muni.cz. FAU - Svobodova, Radka AU - Svobodova R AD - 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. FAU - Olejarova, Marta AU - Olejarova M AD - 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. FAU - Husakova, Marketa AU - Husakova M AD - 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. FAU - Ciferska, Hana AU - Ciferska H AD - 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. FAU - Hulejova, Hana AU - Hulejova H AD - 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. FAU - Tomcik, Michal AU - Tomcik M AD - 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. FAU - Senolt, Ladislav AU - Senolt L AD - 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. FAU - Vencovsky, Jiri AU - Vencovsky J AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151125 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (Biomarkers) RN - 0 (Immunosuppressive Agents) RN - 0 (Tenascin) SB - IM MH - Adult MH - Biomarkers/*blood MH - Cohort Studies MH - Cross-Sectional Studies MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Humans MH - Immunosuppressive Agents/therapeutic use MH - Lupus Erythematosus, Systemic/*blood/drug therapy MH - Male MH - Middle Aged MH - Predictive Value of Tests MH - Prospective Studies MH - Tenascin/*blood PMC - PMC4660660 EDAT- 2015/11/27 06:00 MHDA- 2016/09/08 06:00 PMCR- 2015/11/25 CRDT- 2015/11/27 06:00 PHST- 2015/08/26 00:00 [received] PHST- 2015/11/13 00:00 [accepted] PHST- 2015/11/27 06:00 [entrez] PHST- 2015/11/27 06:00 [pubmed] PHST- 2016/09/08 06:00 [medline] PHST- 2015/11/25 00:00 [pmc-release] AID - 10.1186/s13075-015-0862-4 [pii] AID - 862 [pii] AID - 10.1186/s13075-015-0862-4 [doi] PST - epublish SO - Arthritis Res Ther. 2015 Nov 25;17:341. doi: 10.1186/s13075-015-0862-4.