Expression of herpesvirus entry mediator gene as a Potential Biomarker for Disease Severity in Patients with Persistent Asthma.

Objectives: Herpes virus entry mediator (HVEM) is a costimulatory molecule, and has been proved to play an important role in airway inflammatory and remodeling processes of asthma. We aimed to investigate the expression of HVEM gene in patients with asthma as a means of assessing disease severity.Methods: This study was carried out on 59 subjects, 16 patients with mild persistent asthma, 11 patients with moderate persistent asthma, 13 patients with severe persistent asthma, and 19 age and gender matched healthy controls. The HVEM mRNA expressions of all subjects were determined by real time PCR. Correlations between HVEM mRNA expression and fractional exhaled nitric oxide (FeNO), pulmonary function test values, total blood white cell count and differential, total immunoglobulin E (IgE) level, and Asthma Control Test (ACT) score were analyzed, respectively. The discrimination abilities of HVEM mRNA between different groups were tested using receiver operating characteristics (ROC) curve analyses.Results: This study showed the expressions of HVEM mRNA were significantly higher in the patients with severe and moderate persistent asthma than in patients with mild persistent asthma and healthy subjects (2.97 +/- 1.23 vs. 1.17 +/- 0.42 vs. 0.62 +/- 0.38 vs. 0.46 +/- 0.18/NAPDH, p < 0.001), but there was no significant difference between patients with mild persistent asthma and health controls (0.62 +/- 0.38 vs. 0.46 +/- 0.18/NAPDH, p = 0.557). HVEM mRNA expression at cut off point [1.01/NAPDH, area under the ROC curve (AUC) = 0.99] is sufficient to discriminate severe patients from mild-to-moderate patients, and at cut off point (0.93/NAPDH, AUC = 0.91) for discrimination of moderate-to-severe patients from mild ones, while at cut off point (0.76/NAPDH, AUC = 0.75) for discrimination of asthmatic patients from controls. Furthermore, HVEM mRNA expression was positively correlated with FeNO level (r = 0.524, p = 0.015), and total lymphocyte count (r = 0.426, p = 0.017) in patients with persistent asthma.Conclusions: HVEM gene expressions can be used as a potential biomarker for evaluating the severity of patients with persistent asthma.