Endotyping Eosinophilic Inflammation in COPD with ELAVL1, ZfP36 and HNRNPD mRNA Genes

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a common disease characterized by progressive airflow obstruction, influenced by genetic and environmental factors. Eosinophils have been implicated in COPD pathogenesis, prompting the categorization into eosinophilic and non-eosinophilic endotypes. This study explores the association between eosinophilic inflammation and mRNA expression of ELAVL1, ZfP36, and HNRNPD genes, which encode HuR, TTP and AUF-1 proteins, respectively. Additionally, it investigates the expression of IL-9 and IL-33 in COPD patients with distinct eosinophilic profiles. Understanding these molecular associations could offer insights into COPD heterogeneity and provide potential therapeutic targets. Methods: We investigated 50 COPD patients, of whom 21 had eosinophilic inflammation and 29 had non-eosinophilic inflammation. Epidemiological data, comorbidities, and pulmonary function tests were recorded. Peripheral blood mononuclear cells were isolated for mRNA analysis of ELAVL1, ZfP36, and HNRNPD genes and serum cytokines (IL-9, IL-33) were measured using ELISA kits. Results: The study comprised 50 participants, with 66% being male and a mean age of 68 years (SD: 8.9 years). Analysis of ELAVL1 gene expression revealed a 0.45-fold increase in non-eosinophilic and a 3.93-fold increase in eosinophilic inflammation (p = 0.11). For the ZfP36 gene, expression was 6.19-fold higher in non-eosinophilic and 119.4-fold higher in eosinophilic groups (p = 0.07). Similarly, HNRNPD gene expression was 0.23-fold higher in non-eosinophilic and 0.72-fold higher in eosinophilic inflammation (p = 0.06). Furthermore, serum levels of IL-9 showed no statistically significant difference between the eosinophilic and non-eosinophilic group (58.03 pg/mL vs. 52.55 pg/mL, p = 0.98). Additionally, there was no significant difference in IL-33 serum levels between COPD patients with eosinophilic inflammation and those with non-eosinophilic inflammation (39.61 pg/mL vs. 37.94 pg/mL, p = 0.72). Conclusions: The data suggest a notable trend, lacking statistical significance, towards higher mRNA expression for the ZfP36 and HNRNPD genes for COPD patients with eosinophilic inflammation compared to those with non-eosinophilic inflammation.