IFT46 Expression in the Nasal Mucosa of Primary Ciliary Dyskinesia Patients: Preliminary Study

Manuel Mata; Javier Zurriaga; Lara Milian; Ana Reula; Miguel Armengot; Amparo Ruiz-Sauri; Carmen Carda

doi:10.1177/2152656721989288

IFT46 Expression in the Nasal Mucosa of Primary Ciliary Dyskinesia Patients: Preliminary Study

Allergy Rhinol (Providence). 2021 Feb 11:12:2152656721989288. doi: 10.1177/2152656721989288. eCollection 2021 Jan-Dec.

Authors

Manuel Mata^{1

2

3}, Javier Zurriaga², Lara Milian^{1

2}, Ana Reula^{1

4

5}, Miguel Armengot^{3

4

6

7}, Amparo Ruiz-Sauri^{1

2}, Carmen Carda^{1

2}

Affiliations

¹ Pathology Department, Faculty of Medicine, University of Valencia, Valencia, Spain.
² Research Institute of the University Clinical Hospital of Valencia (INCLIVA), Valencia, Spain.
³ Networking Research Center on Respiratory Diseases (CIBERER), Mallorca, Illes Balears, Spain.
⁴ Grupo de Biomedicina Molecular, Celular y Genómica IIS La Fe, Valencia, Spain.
⁵ Biomedical Sciences Department, Faculty of Health Sciences, CEU-Cardenal Herrera University, Valencia, Spain.
⁶ Surgery Department, Faculty of Medicine, University of Valencia, Valencia, Spain.
⁷ ENT Service, University and Polytechnic Hospital La Fe, Valencia, Spain.

Abstract

Background: Primary ciliary dyskinesia (PCD) is characterised by an imbalance in mucociliary clearance leading to chronic respiratory infections. Cilia length is considered to be a contributing factor in cilia movement. Recently, IFT46 protein has been related to cilia length. Therefore, this work aims to study IFT46 expression in a PCD patients cohort and analyse its relationship with cilia length and function, as it was not previously described.

Materials and methods: The expression of one intraflagellar transport (IFT46) and two regulating ciliary architecture (FOXJ1 and DNAI2) genes, as well as cilia length of 27 PCD patients, were measured. PCD patients were diagnosed based on clinical data, and cilia function and ultrastructure. Gene expression was estimated by real-time RT-PCR and cilia length by electron microscopy in nasal epithelium biopsies.Results and conclusions: While IFT46 expression was only diminished in patients with short cilia, FOXJ1, and DNAI2 expression were reduced in all PCD patient groups compared to controls levels. Among the PCD patients, cilia were short in 44% (5.9 ± 0.70 µm); nine of these (33% from the total) patients' cilia also had an abnormal ultrastructure. Cilia length was normal in 33% of patients (6.4 ± 0.39 µm), and only three patients' biopsies indicated decreased expression of dynein.

Keywords: IFT46; cilia length; ciliogenesis; ciliopathies; primary ciliary dyskinesia.