Nourkami-Tutdibi Nasenien, Freitag Klemens, Zemlin Michael, Tutdibi Erol
Saarland University Medical Center, Hospital for General Pediatrics and Neonatology, Homburg, Germany.
Front Immunol. 2021 Feb 19;12:587313. doi: 10.3389/fimmu.2021.587313. eCollection 2021.
(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. 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. Patients age, gender, and PA status did not affect MBL and SFTPD serum concentrations. MBL concentrations were correlated with MBL haplotypes. Patients with chronic infection (PAC) and MBL insufficiency had a shorter interval between first PA infection and onset of PAC (0.01 vs. 4.6 years, < 0.04) as well as a lower median age at transition to PAC (9.8 vs. 16.4 years, < 0.03) compared to MBL sufficient patients with PAC. SFTPD serum level and FEV1% (Spearman = -0.41, < 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), < 0.04]. 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.
囊性纤维化（CF）中的铜绿假单胞菌（PA）感染与预后不良相关。表面活性蛋白-D（SFTPD）和甘露糖结合凝集素（MBL）在先天免疫和对细菌感染的反应中起关键作用。我们研究了CF患者中SFTPD和MBL的血清水平及基因变异。对35名ΔF508del纯合的白种人患者进行基因分型，检测MBL2（启动子-221 Y/X以及密码子52、54和57）和SFTPD基因（Met11Thr、Ala160Thr和Ser270Thr）内的功能相关多态性。凝集素的血清水平、临床特征和PA状态与基因数据相关。患者的年龄、性别和PA状态不影响MBL和SFTPD的血清浓度。MBL浓度与MBL单倍型相关。与MBL充足的PA慢性感染（PAC）患者相比，慢性感染（PAC）且MBL不足的患者首次PA感染至PAC发病的间隔时间更短（0.01年对4.6年，<0.04），且转变为PAC时的中位年龄更低（9.8岁对16.4岁，<0.03）。无论PA感染状态如何，SFTPD血清水平与第一秒用力呼气容积百分比（FEV1%）均呈负相关（Spearman相关系数=-0.41，<0.03）。与常见的11Met-160Thr-270Ser单倍型携带者相比，SFTPD单倍型11Thr-160Ala-270Ser携带者获得PA的风险比增加[风险比3.0（95%置信区间：1.1-至8.6），<0.04]。MBL不足导致首次PA感染至慢性感染发病的间隔时间缩短。获得PA的易感性与SFTPD基因变异相关，11Thr-160Ala-270Ser作为早期PA感染的风险单倍型。这可能是由于苏氨酸的存在与SFTPD的寡聚结构及与细菌的结合能力有关。
