Academic Department of Paediatrics, Royal Alexandra Children's Hospital, University Hospitals Sussex NHS Foundation Trust, Brighton, UK.
Brighton and Sussex Medical School, Brighton, UK.
Pediatr Pulmonol. 2022 Nov;57(11):2824-2833. doi: 10.1002/ppul.26109. Epub 2022 Aug 30.
Mannose-binding lectin (MBL) is an important component of the innate immune system. Polymorphisms in the MBL2 gene and promoter region are directly associated with MBL-deficiency. We sought to determine the association between MBL genotype on the frequency of common childhood respiratory infections, respiratory symptoms, and atopic outcomes in early childhood.
MBL2 gene variants were analyzed in newborns recruited to the GO-CHILD multicenter prospective cohort study. Follow-up for respiratory infection and atopy diagnoses and symptoms, healthcare utilization, and medication prescription were conducted by postal questionnaires at 12 and 24 months.
Genotyping and follow-up were completed in 1004 children. Genotypes associated with MBL-deficiency were associated with an increased risk of bronchiolitis (relative risk [RR] 1.95, 95% confidence interval [CI] 1.33-2.85) and pneumonia (RR 2.46, 95% CI 1.16-5.22). MBL-deficient genotypes were associated with an increased risk of wheeze with shortness of breath episodes (RR 1.22, 95% CI 1.04-1.43), emergency department attendance (RR 1.90 95% CI 1.13-3.19), and hospital admission (RR 2.01, 95% CI 1.04-3.89) for wheeze. MBL-deficient genotypes were associated with a reduced risk of developing atopic dermatitis (RR 0.72, 95% CI 0.53-0.98).
The positive association between MBL-deficient genotypes and bronchiolitis and pneumonia, as well as a severe wheeze phenotype in some young children, supports the hypothesis that MBL is an important component of innate immunity in the vulnerable period before the maturation of the adaptive immune system. Identification of disease-modifying genotypes may help target preventative strategies in high-risk infants.
甘露糖结合凝集素（MBL）是先天免疫系统的重要组成部分。MBL2 基因和启动子区域的多态性与 MBL 缺乏直接相关。我们旨在确定 MBL 基因型与儿童期常见呼吸道感染、呼吸道症状和特应性结局的频率之间的关联。
在多中心前瞻性 GO-CHILD 队列研究中招募新生儿，分析 MBL2 基因变异。通过在 12 个月和 24 个月时的邮寄问卷，对呼吸道感染和特应性诊断和症状、医疗保健利用和药物处方进行随访。
在 1004 名儿童中完成了基因分型和随访。与 MBL 缺乏相关的基因型与细支气管炎（相对风险 [RR] 1.95，95%置信区间 [CI] 1.33-2.85）和肺炎（RR 2.46，95%CI 1.16-5.22）的风险增加相关。MBL 缺乏的基因型与伴有呼吸急促的喘息发作（RR 1.22，95%CI 1.04-1.43）、急诊就诊（RR 1.90，95%CI 1.13-3.19）和因喘息住院（RR 2.01，95%CI 1.04-3.89）的风险增加相关。MBL 缺乏的基因型与特应性皮炎的发病风险降低相关（RR 0.72，95%CI 0.53-0.98）。
MBL 缺乏基因型与细支气管炎和肺炎之间的正相关，以及一些幼儿中严重的喘息表型，支持 MBL 是适应性免疫系统成熟前易损期先天免疫的重要组成部分的假说。确定疾病修饰基因型可能有助于针对高危婴儿的预防策略。
