van der Starre Willize E, van Nieuwkoop Cees, Thomson Uginia, Zijderveld-Voshart Marleen S M, Koopman Jan Pieter R, van der Reijden Tanny J K, van Dissel Jaap T, van de Vosse Esther
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands; Department of Internal Medicine, Haga Hospital, the Hague, The Netherlands.
PLoS One. 2015 Mar 25;10(3):e0121302. doi: 10.1371/journal.pone.0121302. eCollection 2015.
OBJECTIVE/PURPOSE: Febrile urinary tract infection (UTI) is a common bacterial disease that may lead to substantial morbidity and mortality especially among the elderly. Little is known about biomarkers that predict a complicated course. Our aim was to determine the role of certain urinary cytokines or antimicrobial proteins, plasma vitamin D level, and genetic variation in host defense of febrile UTI and its relation with bacteremia.
A case-control study. Out of a cohort of consecutive adults with febrile UTI (n = 787) included in a multi-center observational cohort study, 46 cases with bacteremic E.coli UTI and 45 cases with non-bacteremic E.coli UTI were randomly selected and compared to 46 controls. Urinary IL-6, IL-8, LL37, β-defensin 2 and uromodulin as well as plasma 25-hydroxyvitamin D were measured. In 440 controls and 707 UTI patients polymorphisms were genotyped in the genes CXCR1, DEFA4, DEFB1, IL6, IL8, MYD88, UMOD, TIRAP, TLR1, TLR2, TLR5 and TNF.
IL-6, IL-8, and LL37 are different between controls and UTI patients, although these proteins do not distinguish between patients with and without bacteremia. While uromodulin did not differ between groups, inability to produce uromodulin is more common in patients with bacteremia. Most participants in the study, including the controls, had insufficient vitamin D and, at least in winter, UTI patients have lower vitamin D than controls. Associations were found between the CC genotype of IL6 SNP rs1800795 and occurrence of bacteremia and between TLR5 SNP rs5744168 and protection from UTI. The rare GG genotype of IL6 SNP rs1800795 was associated with higher β-defensin 2 production.
Although no biomarker was able to distinguish between UTI with or without bacteremia, two risk factors for bacteremia were identified. These were inability to produce uromodulin and an IL6 rs1800795 genotype.
发热性尿路感染（UTI）是一种常见的细菌性疾病，尤其在老年人中可能导致严重的发病率和死亡率。关于预测复杂病程的生物标志物知之甚少。我们的目的是确定某些尿细胞因子或抗菌蛋白、血浆维生素D水平以及基因变异在发热性UTI宿主防御中的作用及其与菌血症的关系。
一项病例对照研究。在一项多中心观察性队列研究中纳入的连续发热性UTI成年人群（n = 787）中，随机选择46例大肠埃希菌菌血症性UTI患者和45例非菌血症性大肠埃希菌UTI患者，并与46例对照进行比较。检测尿白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、LL37、β-防御素2和尿调节蛋白以及血浆25-羟维生素D。在440例对照和707例UTI患者中，对CXCR1、DEFA4、DEFB1、IL6、IL8、MYD88、UMOD、TIRAP、TLR1、TLR2、TLR5和TNF基因的多态性进行基因分型。
对照组和UTI患者之间的IL-6、IL-8和LL37存在差异，尽管这些蛋白质无法区分有无菌血症的患者。虽然尿调节蛋白在各组之间没有差异，但无法产生尿调节蛋白在菌血症患者中更为常见。研究中的大多数参与者，包括对照组，维生素D水平不足，并且至少在冬季，UTI患者的维生素D水平低于对照组。发现IL6 SNP rs1800795的CC基因型与菌血症的发生之间以及TLR5 SNP rs5744168与预防UTI之间存在关联。IL6 SNP rs1800795罕见的GG基因型与较高的β-防御素2产生有关。
虽然没有生物标志物能够区分有无菌血症的UTI，但确定了菌血症的两个危险因素。这些因素是无法产生尿调节蛋白和IL6 rs1800795基因型。
