Expression of the herpes virus entry mediator (HVEM) gene is associated with disease activity in patients with asthma and may, therefore, be a potential biomarker of asthma severity, according to study results published in the Journal of Asthma.

HVEM is a newly discovered costimulatory molecule that may play an important role in the pathophysiology of asthma. Researchers hypothesize that HVEM expression may be a relevant marker of airway inflammation and remodeling that contributes to severe asthma. The objective of this study was to evaluate HVEM gene expressions in patients with asthma and determine its association with disease severity.

Researchers evaluated a total of 59 patients: 16 with mild persistent asthma, 11 with moderate persistent asthma, 13 with severe persistent asthma, and 19 healthy control individuals matched for age and gender. All patients underwent a pulmonary function test, fractional exhaled nitric oxide (FeNO) test, and real-time polymerase chain reaction to assess HVEM messenger ribonucleic acid (mRNA) expressions. The researchers collected and analyzed the following data from patients with asthma: Asthma Control Test score, total blood white cell count, FeNO values, total immunoglobulin E level, and pulmonary function test values. Receiver operating characteristics curve analyses were used to determine the correlation between HVEM mRNA expressions for each group of patients.

HVEM mRNA expressions were significantly higher in patients with severe and moderate persistent asthma (2.97±1.23 vs 1.17±0.42/NAPDH; P <.001) than in patients with mild persistent asthma and healthy control individuals (0.62±0.38 vs 0.46±0.18/NAPDH; P <.001). No significant difference was observed between patients with mild persistent asthma and healthy controls (P =.557). There was a statistically significant difference in FeNO level in patients with mild, moderate, and severe persistent asthma (33.45±7.51 ppb vs 90.00±32.74 ppb vs 106.00±22.19 ppb, respectively; P <.001). In patients with persistent asthma, HVEM mRNA expression was positively correlated with FeNO level (r=0.524; P =.015), and total lymphocyte count (r=0.426; P =.017).

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HVEM expression at cutoff point (1.01/NAPDH; area under the receiver operating characteristics curve [AUC], 0.99) was sufficient to differentiate patients with severe asthma from patients with mild to moderate asthma, and at cutoff point (0.93/NAPDH; AUC, 0.91) to differentiate patients with moderate to severe asthma from patients with mild asthma, although HVEM expression at cutoff point (0.76/NAPDH; AUC, 0.75) could differentiate patients with asthma from healthy controls with a sensitivity and specificity of 67.7% and 100%, respectively. 

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The main limitation of this study was its relatively small cohort size.

The study researchers concluded that HVEM gene expression is significantly higher in patients with persistent asthma and may be a potentially useful biomarker in the evaluation of asthma severity.


Xiong Y, Li B, Zhang Y, et al. Expression of herpesvirus entry mediator gene as a potential biomarker for disease severity in patients with persistent asthma [published online February 21, 2020]. J Asthma. doi:10.1080/02770903.2020.1729382