Association of Immunoglobulin E With Right Ventricular Dysfunction in Pulmonary Arterial Hypertension

Fengxia Wu, Xing Chen, Keren Chen, Jingrong Wei, Chen Gong, Weifeng Wu

https://doi.org/10.1002/pul2.70263 

Abstract

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vasoconstriction and vascular remodeling, leading to increased pulmonary vascular resistance, pathological right ventricular (RV) remodeling, and ultimately right heart failure and death. RV function and right ventricle–pulmonary artery (RV–PA) coupling are critical determinants of patient prognosis, and echocardiography remains the preferred tool for assessing RV function and predicting RV–PA coupling. Recent studies have revealed that immunoglobulin E(IgE) plays a regulatory role in cardiac and pulmonary vascular remodeling; however, its role in PAH-related RV dysfunction remains unclear. This study aimed to investigate the association between serum IgE levels and RV dysfunction in patients with PAH through echocardiography, serological testing, and right heart catheterization (RHC), to provide potential evidence for novel diagnostic and therapeutic strategies in PAH. A total of 30 patients diagnosed with idiopathic pulmonary arterial hypertension (IPAH) at the First Affiliated Hospital of Chinese Guangxi Medical University between 2024 and 2025 were prospectively enrolled, along with an equal number of age- and sex-matched individuals with normal cardiac function and no cardiopulmonary disease as controls. Clinical baseline data and serum samples were collected from all participants, and serum IgE concentrations were determined using enzyme-linked immunosorbent assay (ELISA). For IPAH patients, serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, RHC parameters, and World Health Organization (WHO) functional class were obtained from the electronic medical record system. Transthoracic echocardiography (TTE) was performed to assess RV morphology, structural characteristics, and functional alterations. Statistical analysis was performed using t-tests, Mann–Whitney U-tests, one-way ANOVA, correlation, and regression analysis to evaluate the differences in IgE levels between groups and the relationship with RV function parameters. The results showed that in the IPAH group, 13 patients (43.3%) were male, with a mean age of 41.27 ± 11.50 years, whereas the control group included 14 males (46.7%) with a mean age of 41.35 ± 10.78 years. Serum IgE levels were significantly higher in IPAH patients compared with controls (859 [702, 1031] vs. 430 [359, 568], ng/mL, p < 0.0001). Correlation analyses based on electronic medical record data demonstrated that serum IgE levels in IPAH patients were positively associated with NT-proBNP concentrations (r = 0.79, p < 0.0001). Moreover, patients in WHO functional class III with right heart failure exhibited significantly higher serum IgE levels than those in functional class I, and IgE levels showed a positive correlation with WHO functional class. Serum IgE levels were also positively correlated with RV pressure and PA pressure (IgE and mPAP: r = 0.37, 95% CI: 0.01–0.64, p = 0.04; IgE and mRVP: r = 0.43, CI: 0.08–0.68, p = 0.01). Echocardiographic analyses further revealed that serum IgE levels were positively correlated with RV hypertrophy and dilation, while being inversely correlated with RV contractile function and TAPSE/sPAP (r = −0.72 [−0.86, −0.49], p < 0.0001). Comparisons across groups indicated that serum IgE levels were significantly elevated in IPAH patients whose RV remodeling had progressed to the maladaptive phase compared with those in the adaptive phase (984 [834, 1110] vs. 684 [612, 861], ng/mL, p < 0.0001). This study demonstrated that serum IgE levels were significantly elevated in patients with PAH and positively correlated with the severity of RV dysfunction. Notably, the marked increase in IgE levels predominantly occurred during the maladaptive phase of RV remodeling after RV–PA uncoupling. These findings suggest that IgE-mediated immune mechanisms may contribute to the progression of right heart failure in PAH. Serum IgE holds potential as a diagnostic biomarker for PAH-related right heart failure, and anti-IgE therapy may represent a promising therapeutic strategy that warrants further investigation.

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