Luis Pablo Gravina1, Carolina Crespo1, Hilda Giugno2, Luisa Sen3, Lilien Chertkoff1, Andrea Mangano3, Claudio Castaños2. 1. Laboratorio de Biología Molecular, Servicio de Genética, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan", Buenos Aires, Argentina. 2. Servicio de Neumonología, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan", Buenos Aires, Argentina. 3. Laboratorio de Biología Celular y Retrovirus, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan", CONICET, Buenos Aires, Argentina.
Abstract
BACKGROUND: There is a considerable variation in the phenotype and course of the disease in cystic fibrosis (CF) even in patients with the same CFTR genotype, suggesting that other factors are important for prognosis. Mannose-binding lectin (MBL) has been proposed as one of these factors. We therefore investigated the influence of MBL2 gene variants on disease severity, age at acquisition of Pseudomonas aeruginosa, and survival in CF patients. METHODS: MBL2 variants were studied in 106 Argentinean pediatric CF patients carrying two severe CFTR mutations. Clinical phenotype was defined according to the Shwachman score and lung function tests. Age at infection with P. aeruginosa and age at death were also recorded. RESULTS: MBL insufficiency was associated with a 3.5-fold risk of having a severe phenotype (CI 95%: 1.2-10.3, p=0.03). It was also associated with an earlier onset of infection with P. aeruginosa (p=0.035). No statistically significant differences were found in FEV1 and survival. CONCLUSIONS: MBL insufficiency was associated with detrimental progression of the disease. These results together with previous findings suggest that the effect of MBL2 expression may be a major determinant of the severity of the clinical phenotype in patients with CF.
BACKGROUND: There is a considerable variation in the phenotype and course of the disease in cystic fibrosis (CF) even in patients with the same CFTR genotype, suggesting that other factors are important for prognosis. Mannose-binding lectin (MBL) has been proposed as one of these factors. We therefore investigated the influence of MBL2 gene variants on disease severity, age at acquisition of Pseudomonas aeruginosa, and survival in CFpatients. METHODS:MBL2 variants were studied in 106 Argentinean pediatric CFpatients carrying two severe CFTR mutations. Clinical phenotype was defined according to the Shwachman score and lung function tests. Age at infection with P. aeruginosa and age at death were also recorded. RESULTS:MBL insufficiency was associated with a 3.5-fold risk of having a severe phenotype (CI 95%: 1.2-10.3, p=0.03). It was also associated with an earlier onset of infection with P. aeruginosa (p=0.035). No statistically significant differences were found in FEV1 and survival. CONCLUSIONS:MBL insufficiency was associated with detrimental progression of the disease. These results together with previous findings suggest that the effect of MBL2 expression may be a major determinant of the severity of the clinical phenotype in patients with CF.
Authors: Melissa A Wilk; Andrew T Braun; Philip M Farrell; Anita Laxova; Donna M Brown; James M Holt; Camille L Birch; Nadiya Sosonkina; Brandon M Wilk; Elizabeth A Worthey Journal: Cold Spring Harb Mol Case Stud Date: 2020-02-03