A range of 30%-62% of functioning multiciliated airway cells is sufficient to maintain ciliary airway clearance.

DNAAF6 X-chromosome inactivation ciliary clearance primary ciliary dyskinesia

Journal

The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460

Informations de publication

Date de publication:
11 Jul 2024
Historique:
medline: 12 7 2024
pubmed: 12 7 2024
entrez: 11 7 2024
Statut: aheadofprint

Résumé

Primary ciliary dyskinesia (PCD) is a genetic disorder caused by aberrant motile cilia function that results in defective ciliary airway clearance and subsequently to recurrent airway infections and bronchiectasis. How many functional multiciliated airway cells are sufficient to maintain ciliary airway clearance? To answer this question we exploited the molecular defects of the X-linked recessive PCD variant caused by pathogenic variants in PCD males with hemizygous pathogenic Our findings indicate that 30%-62% of functioning multiciliated respiratory cells are able to generate either normal or slightly reduced ciliary clearance. Because heterozygous females displayed either no or subtle respiratory symptoms, complete correction of 30% of cells by precision medicine might be able to improve ciliary airway clearance in PCD individuals as well as clinical symptoms.

Sections du résumé

BACKGROUND BACKGROUND
Primary ciliary dyskinesia (PCD) is a genetic disorder caused by aberrant motile cilia function that results in defective ciliary airway clearance and subsequently to recurrent airway infections and bronchiectasis.
QUESTION OBJECTIVE
How many functional multiciliated airway cells are sufficient to maintain ciliary airway clearance?
METHODS METHODS
To answer this question we exploited the molecular defects of the X-linked recessive PCD variant caused by pathogenic variants in
RESULTS RESULTS
PCD males with hemizygous pathogenic
CONCLUSIONS CONCLUSIONS
Our findings indicate that 30%-62% of functioning multiciliated respiratory cells are able to generate either normal or slightly reduced ciliary clearance. Because heterozygous females displayed either no or subtle respiratory symptoms, complete correction of 30% of cells by precision medicine might be able to improve ciliary airway clearance in PCD individuals as well as clinical symptoms.

Identifiants

pubmed: 38991708
pii: 13993003.01441-2023
doi: 10.1183/13993003.01441-2023
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.

Auteurs

Niki T Loges (NT)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

June Kehlet Marthin (JK)

Danish PCD Centre, Danish Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Johanna Raidt (J)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Heike Olbrich (H)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Inga M Höben (IM)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Sandra Cindric (S)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Diana Bracht (D)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Julia König (J)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Cynthia Rieck (C)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Sebastian George (S)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Tim Luis Kloth (TL)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Kai Wohlgemuth (K)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Petra Pennekamp (P)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Bernd Dworniczak (B)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Mathias G Holgersen (MG)

Danish PCD Centre, Danish Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Jobst Römel (J)

Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Christian Schmalstieg (C)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Isabella Aprea (I)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Jann Mortensen (J)

Danish PCD Centre, Danish Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Kim G Nielsen (KG)

Danish PCD Centre, Danish Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Heymut Omran (H)

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany. Heymut.Omran@ukmuenster.de.

Classifications MeSH