Chong Yong Pil, Park Ki-Ho, Kim Eun Sil, Kim Mi-Na, Kim Sung-Han, Lee Sang-Oh, Choi Sang-Ho, Jeong Jin-Yong, Woo Jun Hee, Kim Yang Soo
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Center for Antimicrobial Resistance and Microbial Genetics, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Division of Infectious Diseases, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
PLoS One. 2014 Mar 4;9(3):e89139. doi: 10.1371/journal.pone.0089139. eCollection 2014.
Mannose-binding lectin (MBL) is an important component of innate immunity. Structural and promoter polymorphisms in the MBL2 gene that are responsible for low MBL levels are associated with susceptibility to infectious diseases. The objective of this study was to investigate the association of serum MBL levels and MBL2 polymorphisms with persistent Staphylococcus aureus bacteremia (SAB) in adult Korean patients.
We conducted a case-control study nested in a prospective cohort of patients with SAB. The study compared 41 patients with persistent bacteremia (≥7 days) and 46 patients with resolving bacteremia (<3 days). In each subject, we genotyped six single-nucleotide polymorphisms in the promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (alleles A/B, A/C, and A/D) of the MBL2 gene and measured serum MBL concentrations. We also compared MBL2 genotypes between SAB patients and healthy people.
Patients with persistent bacteremia were significantly more likely to have low/deficient MBL-producing genotypes and resultant low serum MBL levels, than were patients with resolving bacteremia (P = 0.019 and P = 0.012, respectively). Independent risk factors for persistent bacteremia were metastatic infection (adjusted odds ratio [aOR], 34.7; 95% confidence interval [CI], 12.83-196.37; P = 0.003), methicillin resistance (aOR, 4.10; 95% CI, 3.19-29.57; P = 0.025), and low/deficient MBL-producing genotypes (aOR, 7.64; 95% CI, 4.12-63.39; P = 0.003). Such genotypes were significantly more common in patients with persistent bacteremia than in healthy people (OR, 2.09; 95% CI, 1.03-4.26; P = 0.040).
This is the first demonstration of an association of low MBL levels and MBL2 polymorphisms responsible for low or deficient MBL levels with persistent SAB. A combination of factors, including clinical and microbiological characteristics and host defense factors such as MBL levels, may together contribute to the development of persistent SAB.
甘露糖结合凝集素（MBL）是固有免疫的重要组成部分。MBL2基因中导致MBL水平低下的结构和启动子多态性与传染病易感性相关。本研究的目的是调查韩国成年患者血清MBL水平和MBL2多态性与持续性金黄色葡萄球菌菌血症（SAB）之间的关联。
我们在一个SAB患者前瞻性队列中进行了一项病例对照研究。该研究比较了41例持续性菌血症（≥7天）患者和46例菌血症缓解患者（<3天）。在每个受试者中，我们对MBL2基因启动子区域（等位基因H/L、X/Y和P/Q）和外显子1（等位基因A/B、A/C和A/D）中的6个单核苷酸多态性进行基因分型，并测量血清MBL浓度。我们还比较了SAB患者和健康人之间的MBL2基因型。
与菌血症缓解患者相比，持续性菌血症患者更有可能具有低/缺乏MBL产生的基因型以及由此导致的低血清MBL水平（分别为P = 0.019和P = 0.012）。持续性菌血症的独立危险因素包括转移性感染（调整后的优势比[aOR]，34.7；95%置信区间[CI]，12.83 - 196.37；P = 0.003）、耐甲氧西林（aOR，4.10；95% CI，3.19 - 29.57；P = 0.025）以及低/缺乏MBL产生的基因型（aOR，7.64；95% CI，4.12 - 63.39；P = 0.003）。这些基因型在持续性菌血症患者中显著比健康人更常见（OR，2.09；95% CI，1.03 - 4.26；P = 0.040）。
这是首次证明低MBL水平以及导致MBL水平低或缺乏的MBL2多态性与持续性SAB之间存在关联。包括临床和微生物学特征以及宿主防御因素（如MBL水平）在内的多种因素可能共同促成持续性SAB的发生。
