Serum autophagy protein 5 is positively related to T helper 2/T helper 1 ratio, inflammation, and exacerbation in adult asthma patients

Abstract

Background: Autophagy protein 5 (ATG5) regulates airway epithelial cell autophagy, immune response, and inflammation, which is involved in asthma progression. This study aimed to evaluate ATG5 levels and its clinical roles in adult asthma patients.

Methods: Totally, 200 adult asthma patients and 100 healthy controls (HCs) were enrolled in this case-control study. Subsequently, serum ATG5 was measured by enzyme-linked immunosorbent assay.

Results: ATG5 was increased in asthma patients compared with HCs [median (interquartile range): 44.2 (31.7-77.8) vs. 23.2 (16.7-39.2) ng/mL] (P < 0.001). In asthma patients, ATG5 was positively related to male gender (P = 0.022), a family history of asthma (P = 0.035), eosinophil count (P < 0.001), and immune globulin E (P < 0.001), while it was negatively correlated with forced expiratory volume in 1 s (FEV₁)/forced vital capacity (P < 0.001) and FEV₁ (Predicted) (P < 0.001). Meanwhile, ATG5 was inversely associated with T helper (Th) 1 cells (P = 0.008), while it was positively linked with Th2 cells (P < 0.001), Th2/Th1 ratio (P < 0.001), interleukin (IL)-4 (P = 0.002), and IL-4/interferon-γ ratio (P = 0.015). Additionally, ATG5 was positively correlated with tumor necrosis factor-α (P < 0.001), IL-1β (P = 0.001), IL-6 (P = 0.003), and IL-17 (P = 0.029). Notably, ATG5 was elevated in asthma patients at exacerbation compared to those at remission [median (interquartile range): 53.6 (37.6-90.0) vs. 35.6 (28.2-51.5) ng/mL] (P < 0.001). It was also noteworthy that ATG5 was positively linked with exacerbation severity in asthma patients (P = 0.005).

Conclusion: Serum ATG5 is related to increased Th2/Th1 ratio, inflammation, exacerbation risk and severity in adult asthma patients, which serves as a candidate marker for the management of asthma. However, further validation is still needed.

Keywords: Asthma; Autophagy protein 5; Exacerbation; Inflammation; T helper cell.

Fig. 1

ATG5 in adult asthma patients and HCs. Comparison of ATG5 (skewed distributed continuous data) between adult asthma patients and HCs (Wilcoxon rank sum test) (A); ROC curve showing the ability of ATG5 (skewed distributed continuous data) to distinguish adult asthma patients from HCs (ROC curve) (B)

Fig. 2

Relationship of ATG5 with clinical features in adult asthma patients. The association of ATG5 (skewed distributed continuous data) with age (normal distributed continuous data, Spearman’s rank correlation test) (A), gender (categorized data, Wilcoxon rank sum test) (B), family history of asthma (categorized data, Wilcoxon rank sum test) (C), history of allergic rhinitis (categorized data, Wilcoxon rank sum test) (D), eosinophil count (skewed distributed continuous data, Spearman’s rank correlation test) (E), IgE (skewed distributed continuous data, Spearman’s rank correlation test) (F), FEV₁/FVC (normal distributed continuous data, Spearman’s rank correlation test) (G), and FEV₁ (Predicted) (normal distributed continuous data, Spearman’s rank correlation test) (H) in adult asthma patients

Fig. 3

Relationship of ATG5 with Th1, Th2, and their corresponding cytokines in adult asthma patients. The association of ATG5 (skewed distributed continuous data) with Th1 cells (skewed distributed continuous data, Spearman’s rank correlation test) (A), Th2 cells (skewed distributed continuous data, Spearman’s rank correlation test) (B), Th2/Th1 ratio (skewed distributed continuous data, Spearman’s rank correlation test) (C), IFN-γ (skewed distributed continuous data, Spearman’s rank correlation test) (D), IL-4 (skewed distributed continuous data, Spearman’s rank correlation test) (E), and IL-4/IFN-γ ratio (skewed distributed continuous data, Spearman’s rank correlation test) (F) in adult asthma patients

Fig. 4

Relationship of ATG5 with inflammatory cytokines in adult asthma patients. The association of ATG5 (skewed distributed continuous data) with TNF-α (skewed distributed continuous data, Spearman’s rank correlation test) (A), IL-1β (skewed distributed continuous data, Spearman’s rank correlation test) (B), IL-6 (skewed distributed continuous data, Spearman’s rank correlation test) (C), and IL-17 (skewed distributed continuous data, Spearman’s rank correlation test) (D) in adult asthma patients

Fig. 5

Relationship of ATG5 with exacerbation risk and severity in adult asthma patients. The association of ATG5 (skewed distributed continuous data) with exacerbation risk in adult asthma patients (categorized data, Wilcoxon rank sum test) (A); ROC curve showing the ability of ATG5 (skewed distributed continuous data) to discriminate adult asthma patients at exacerbation from adult asthma patients at remission (ROC curve) (B); the association of ATG5 (skewed distributed continuous data) with exacerbation severity in adult asthma patients (categorized data, Spearman’s rank correlation test) (C)