Multimodal analysis of granulocytes, monocytes, and platelets in patients with cystic fibrosis before and after Elexacaftor–Tezacaftor–Ivacaftor treatment

Schmidt H, Höpfer LM, Wohlgemuth L, Knapp CL, Mohamed AOK, Stukan L, Münnich F, Hüsken D, Koller AS, Stratmann AEP, Müller P, Braun CK, Fabricius D, Bode SFN, Huber-Lang M, Messerer DAC (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 14

Article Number: 1180282

DOI: 10.3389/fimmu.2023.1180282

Abstract

Cystic fibrosis (CF) is a monogenetic disease caused by an impairment of the cystic fibrosis transmembrane conductance regulator (CFTR). CF affects multiple organs and is associated with acute and chronic inflammation. In 2020, Elexacaftor–Tezacaftor–Ivacaftor (ETI) was approved to enhance and restore the remaining CFTR functionality. This study investigates cellular innate immunity, with a focus on neutrophil activation and phenotype, comparing healthy volunteers with patients with CF before (T1, n = 13) and after six months (T2, n = 11) of ETI treatment. ETI treatment reduced sweat chloride (T1: 95 mmol/l (83|108) vs. T2: 32 mmol/l (25|62), p < 0.01, median, first|third quartile) and significantly improved pulmonal function (FEV1 T1: 2.66 l (1.92|3.04) vs. T2: 3.69 l (3.00|4.03), p < 0.01). Moreover, there was a significant decrease in the biomarker human epididymis protein 4 (T1: 6.2 ng/ml (4.6|6.3) vs. T2: 3.0 ng/ml (2.2|3.7), p < 0.01) and a small but significant decrease in matrix metallopeptidase 9 (T1: 45.5 ng/ml (32.5|140.1) vs. T2: 28.2 ng/ml (18.2|33.6), p < 0.05). Neutrophil phenotype (CD10, CD11b, CD62L, and CD66b) and function (radical oxygen species generation, chemotactic and phagocytic activity) remained largely unaffected by ETI treatment. Likewise, monocyte phenotype and markers of platelet activation were similar at T1 and T2. In summary, the present study confirmed a positive impact on patients with CF after ETI treatment. However, neither beneficial nor harmful effects of ETI treatment on cellular innate immunity could be detected, possibly due to the study population consisting of patients with well-controlled CF.

Involved external institutions

Universitätsklinikum Ulm DE Germany (DE)

How to cite

APA:

Schmidt, H., Höpfer, L.M., Wohlgemuth, L., Knapp, C.L., Mohamed, A.O.K., Stukan, L.,... Messerer, D.A.C. (2023). Multimodal analysis of granulocytes, monocytes, and platelets in patients with cystic fibrosis before and after Elexacaftor–Tezacaftor–Ivacaftor treatment. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1180282

MLA:

Schmidt, Hanna, et al. "Multimodal analysis of granulocytes, monocytes, and platelets in patients with cystic fibrosis before and after Elexacaftor–Tezacaftor–Ivacaftor treatment." Frontiers in Immunology 14 (2023).

BibTeX: Download