Work

Genetic Association With Pseudomonas aeruginosa Acquisition in Cystic Fibrosis: Influence of Surfactant Protein D and Mannose-Binding Lectin

Year: 2021

Type: article

Abstract: Background:Pseudomonas aeruginosa(PA) infection in cystic fibrosis (CF) is associated with poor prognosis. Surfactant protein-D (SFTPD) and mannose-binding lectin (MBL) play a critical role in innate immunity and response to bacterial infections. We investigated serum levels and genetic variants of SFTPD and MBL in CF patients. Method:Thirty-five Caucasian patients homozygous for ΔF508del were genotyped for functional relevant polymorphisms within MBL2 (promoter−221 Y/X, codons 52, 54, and 57) and SFTPD genes (Met11Thr, Ala160Thr, and Ser270Thr). Serum levels of collectins, clinical characteristics, and PA status were correlated with genetic data. Results:Patients age, gender, and PA status did not affect MBL and SFTPD serum concentrations. MBL concentrations were correlated with MBL haplotypes. Patients with chronicPseudomonas aeroginosainfection (PAC) and MBL insufficiency had a shorter interval between first PA infection and onset of PAC (0.01 vs. 4.6 years,p< 0.04) as well as a lower median age at transition to PAC (9.8 vs. 16.4 years,p< 0.03) compared to MBL sufficient patients with PAC. SFTPD serum level and FEV1% (Spearmanr= −0.41,p< 0.03) showed a negative correlation irrespective of PA infection status. The hazard ratio to PA acquisition was increased in carriers of the SFTPD haplotype 11Thr-160Ala-270Ser compared to carriers of the common 11Met-160Thr-270Ser haplotype [HR 3.0 (95%CI: 1.1–8.6),p< 0.04]. Conclusion:MBL insufficiency leads to a shorter interval between first PA infection and onset of chronic infection. Susceptibility to PA acquisition is associated with SFTPD genetic variants with 11Thr-160Ala-270Ser as risk haplotype for early PA infection. This may be due to presence of threonine associated with oligomeric structure of SFTPD and binding ability to bacteria.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2021.587313

Authors: Nasenien Nourkami-Tutdibi, Klemens Freitag, Michael Zemlin, Erol Tutdibi

Institution: Universitätsklinikum des Saarlandes

Language: English

Topic: Cystic Fibrosis Research Advances

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,950