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Cyclosporine A in children with ABCA3 deficiency.
Yang, Xiaohua; Forstner, Maria E; Rothenaigner, Ina; Bullo, Marina; Sismanlar, Tugba E; Aslan, Ayse T; Latzin, Philipp; Hadian, Kamyar; Griese, Matthias.
Afiliación
  • Yang X; Dr. von Haunersches Kinderspital, University of Munich, German Center for Lung Research (DZL), Munich, Germany.
  • Forstner ME; Dr. von Haunersches Kinderspital, University of Munich, German Center for Lung Research (DZL), Munich, Germany.
  • Rothenaigner I; Research Unit Signaling and Translation, Helmholtz Zentrum München, Neuherberg, Germany.
  • Bullo M; Pediatric Pneumology and Allergology, University Children´s Inselspital Bern, University of Bern, Bern, Switzerland.
  • Sismanlar TE; Department of Pediatric Pulmonology, Faculty of Medicine, Gazi University, Ankara, Turkey.
  • Aslan AT; Department of Pediatric Pulmonology, Faculty of Medicine, Gazi University, Ankara, Turkey.
  • Latzin P; Pediatric Pneumology and Allergology, University Children´s Inselspital Bern, University of Bern, Bern, Switzerland.
  • Hadian K; Research Unit Signaling and Translation, Helmholtz Zentrum München, Neuherberg, Germany.
  • Griese M; Dr. von Haunersches Kinderspital, University of Munich, German Center for Lung Research (DZL), Munich, Germany.
Pediatr Pulmonol ; 2024 Jul 23.
Article en En | MEDLINE | ID: mdl-39041931
ABSTRACT

BACKGROUND:

Biallelic ATP-binding cassette subfamily A member 3 (ABCA3) variants can cause interstitial lung disease in children and adults, for which no proven treatments exist. Recent in vitro evidence suggested that cyclosporine A (CsA) could correct some ABCA3 variants, however for other variants this is unknown and no data in patients exist.

METHODS:

We retrieved the clinical data of two children aged 2 and 4 years carrying homozygous ABCA3 variants (G210C and Q1045R, respectively) and empiric CsA treatment from the Kids Lung Register database. In vitro experiments functionally characterized the two variants and explored the effects of CsA alone or combined with hydroxychloroquine (HCQ) in a human alveolar epithelial cell line (A549) derived from adenocarcinoma cells.

RESULTS:

Six weeks following the introduction of CsA, both children required a reduced O2 flow supply, which then remained stable on CsA. Later, when CsA was discontinued, the clinical status of the children remained unchanged. Of note, the children simultaneously received prednisolone, azithromycin, and HCQ. In vitro, both ABCA3 variants demonstrated defective lysosomal colocalization and impaired ABCA3+ vesicle size, with proteolytic cleavage impairment only in Q1045R. CsA alone corrected the trafficking impairment and ABCA3+ vesicle size of both variants with a variant-specific effect on phosphatidylcholine recycling in G210C. CsA combined with HCQ were additive for improving trafficking of ABCA3 in G210C, but not in Q1045R.

CONCLUSIONS:

CsA treatment might be helpful for certain patients with ABCA3 deficiency, however, currently strong clinical supporting evidence is lacking. Appropriate trials are necessary to overcome this unmet need.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pediatr Pulmonol Asunto de la revista: PEDIATRIA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pediatr Pulmonol Asunto de la revista: PEDIATRIA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos