Serum 14-3-3β Protein: a New Biomarker in Asthmatic Patients With Acute Attack

Abstract

Background: The determination of systemic inflammatory markers is one of the important directions to study the pathogenesis of asthma and improve the diagnosis of asthma. Current studies have found that the 14-3-3 protein family subtypes interact with target proteins to participate in the pathogenesis of a variety of immune inflammatory diseases. However, studies on serum tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein β (14-3-3β) in asthma are scarce. This study aimed to assess the clinical significance of 14-3-3β in asthmatic patients. Methods: We recruited 54 asthmatic patients with acute attack and 50 asthmatic patients with chronic persistent. The normal control group included 54 healthy individuals with similar sex-age indicators. Clinical characteristics (age, gender, height and weight), clinical indicators [fractional expiratory nitric oxide (FeNO), eosinophil count, forced vital capacity (FVC), percent of predicted FVC (FVC % predicted), forced expiratory volume in one second (FEV1), percent of predicted FEV1 (FEV1% predicted), the ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) and percent of predicted FEV1/FVC (FEV1/FVC% predicted)] and serum 14-3-3β levels were measured to compare among each group. Spearman’s rank correlation coefficient was used to evaluate the correlation between 14-3-3β and clinical indicators. Finally, Receiver-operating characteristic (ROC) curves analysis was used to determine the sensitivity and specificity of 14-3-3β.Results: Our results showed that median (interquartile range) of serum 14-3-3β concentration (ng/ml) in acute attack group of asthma (41.18 [33.06-51.76]) was much higher than that in normal control group (24.99 [17.43-29.91]; P<0.001) and chronic persistent group of asthma (25.88 [21.03-34.55]; P<0.001),however, it was that exist no statistical heterogeneity with regard to the serum 14-3-3β level between the chronic persistent group of asthma and the healthy individuals (P >0.05). Spearman’s correlation coefficient shows that the serum 14-3-3β level was positively correlated with FeNO (r=-0.292, P=0.032) and peripheral blood eosinophil count (r=0.328, P=0.016), and was negatively related to FEV1/FVC (r=-0.293, P=0.031) and FEV1/FVC% predicted (r=-0.299, P=0.028) in the acute attack group of asthma. At the same time, the serum 14-3-3β level was also negatively associated with FEV1 (r=-0.297, P=0.036) in the chronic persistent group of asthma. ROC curve analysis comparing acute attack group of asthma with normal control group demonstrated a significant (P<0.001) AUC of 0.90 (95% CI, 0.85–0.96). When the cut off value was 29.70 ng/ml, the ROC curve yielded a sensitivity of 92.6%, a specificity of 75.9%, a positive likelihood ratio (+LR) of 3.84, negative likelihood ratio (-LR) of 0.10 and a Youden index of 0.69 in acute attack group of asthma. ROC curve analysis comparing chronic persistent group of asthma with normal control group demonstrated no statistically significant difference (P>0.05) AUC of 0.60 (95% CI, 0.49–0.70). Conclusion: The Elevated serum 14-3-3β levels may be associated with airway inflammation and impaired bronchial patency in the acute attack of asthma. The serum 14-3-3β protein can be used to distinguish between asthmatic patients with acute attack and healthy individuals and may become a potential biomarker in asthmatic patients with acute attack.