Two Siblings Homozygous for F508del-CFTR Have Varied Disease Phenotypes and Protein Biomarkers

International Journal of Molecular Sciences

YanhuiH. Zhang¹  Jin Wang²  ElizabethA. Fitzpatrick²  Weiqiang Zhang³  Zhihong Zhang³  ToniaE. Gardner³ 

[1] Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA;Department of Microbiology, Immunology, and Biochemistry, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA;Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA;

关键词: cystic fibrosis (CF);    CFTR;    F508del-CFTR;    disease phenotypes;    infection;    inflammation;   

DOI  :  10.3390/ijms22052631

来源: DOAJ

【 摘 要 】

Two siblings with CF are homozygous for F508del (referred to as Subject A and Subject B). Despite having the same CFTR genotype and similar environment, these two subjects exhibited different disease phenotypes. We analyzed their medical records and CF Foundation Registry data and measured inflammatory protein mediators in their sputum samples. Then, we examined the longitudinal relationships between inflammatory markers and disease severity for each subject and compared between them. Subject A presented a more severe disease than Subject B. During the study period, Subject A had two pulmonary exacerbations (PEs) whereas Subject B had one mild PE. The forced expiratory volume in 1 s (FEV₁, % predicted) values for Subject A were between 34–45% whereas for Subject B varied between 48–90%. Inflammatory protein mediators associated with neutrophils, Th1, Th2, and Th17 responses were elevated in sputum of Subject A compared with Subject B, and also in samples collected prior to and during PEs for both subjects. Neutrophilic elastase (NE) seemed to be the most informative biomarkers. The infectious burden between these two subjects was different.

【 授权许可】

Unknown