Study Identifies Potential Biomarker for SLE

A study in Arthritis Research & Therapy suggests that circulating levels of the proinflammatory glycoprotein tenascin-C (TNC) may be a predictive biomarker in systemic lupus erythematosus (SLE).

The finding is important because the exact etiology of SLE remains poorly understood. The disease manifests in many organs and is characterized by unpredictable flares and remissions. The lack of useful biomarkers for SLE hampers assessment of disease activity and impedes the evaluation of treatment response. Thus, there is substantial interest in finding valid biomarkers to use as surrogate markers of disease activity and/or to predict flares of the disease.

TNC is a protein rarely found in healthy adult tissues, because it is specifically induced and tightly controlled during acute inflammation and persistently expressed during chronic inflammation, according to the researchers. Higher levels of TNC are associated with inflammatory diseases such as pneumonitis, hepatitis, inflammatory bowel disease, and rheumatoid arthritis, among others. But this is the first study to investigate serum TNC levels with SLE Disease Activity Index 2000 (SLEDAI-2K).

The current study analyzed serum TNC levels in 59 SLE patients and in 65 healthy controls. SLE patients were followed for a mean of 11 months, disease activity was assessed using SLEDAI-2 K and British Isles Lupus Assessment Group disease activity index (BILAG-2004), clinical and laboratory data were recorded every 3—6 months. Changes in glucocorticoids (GC) and immunosuppressants (IS) were recorded serially.

There was no significant difference in the mean levels of TNC between the SLE patients and controls. However, in SLE patients with active disease (SLEDAI ≥6), the TNC levels were significantly higher than in the controls (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. The baseline serum TNC level was the single most important independent predictor of flare (i) compared with conventional biomarkers.

“Little or no TNC is found in most healthy adult tissues, but it is upregulated under pathological conditions accompanying tissue injury and inflammation in many different organs that may be involved in the SLE disease process, including the joints, skin, kidney, lungs, heart, and central nervous system,” the authors observed. “ Therefore, TNC seems to be an eligible candidate surrogate marker of ongoing tissue damage and may reflect disease activity or an impending flare.”

Limitations of the study include that it was performed cross-sectionally in a single SLE cohort with a limited number of patients. “Further studies with a larger cohort of patients are required to validate the role of TNC as a useful serum biomarker for monitoring disease activity and predicting flares in patients with SLE,” the authors conclude.