The simultaneous analysis of ATI

The simultaneous analysis of ATI and FC levels shows that the therapeutic escalation is associated to high values of either these variables. Importantly, their impact in the need of a future therapeutic escalation is independent of the disease severity, as is shown by the fact that neither histological score nor endoscopic lesions are significant variables in this context. A combination of a biomarker and ATIs levels to predict disease development has been shown before: in fact, C-reactive fluorescent probes levels combined with IFX-TLs and ATI stability were shown to predict LOR in IBD patients (Roblin et al., 2015). Our results, together with the literature, suggest that high levels of ATIs and FC found in otherwise stable UC patients may indicate a future disease flare and its consequent therapeutic escalation. These findings have some important clinical implications: TDM on stable patients is useful if ATI levels are included and should be performed alongside with FC determination: the presence of elevated ATIs of FC levels – even in the absence of clinical symptoms – should alert the physician to act in order to prevent future therapeutic escalations. In short, this study explores the IFX pharmacokinetics and the utility of drug and disease monitoring among UC patients in remission. Our findings show that, in these patients, IFX clearance is mainly related to the presence of ATIs. Moreover, and irrespective of the IFX regimen, IFX TLs, AUC, clearance and ATI concentration are unable to differentiate patients according to their outcome. Conversely, high ATI levels are significantly associated with the long-term need to undergo therapeutic escalation, as are FC levels above 250μg/g. Therefore, the usefulness of TDM in clinically-stable UC patients relies on the possibility of avoiding future disease progression that can be predicted based on the ATI levels. Moreover, the monitoring of FC should also be carried out in these patients, as this biomarker is also increased in patients that eventually need to undergo a therapeutic escalation. The following are the supplementary data related to this article.
Funding Sources This work was supported by the Portuguese IBD Group (GEDII – Grupo de Estudo da Doença Inflamatória Intestinal). The funder had no role in study design, data collection, data analysis, interpretation and writing of the report.
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Introduction Nutrient acquisition by pathogens during infection is imperative for bacterial proliferation and disease development (Porcheron et al., 2016). The host exploits the nutritional requirements of the pathogen to limit growth by altering the availability of micronutrients at the colonization surface in a process referred to as nutritional immunity (Corbin et al., 2008; Damo et al., 2013; Kehl-Fie and Skaar, 2010; Ong et al., 2014). Although insights into the role of nutritional immunity in host defenses against pathogenic microorganisms are rapidly emerging (Corbin et al., 2008; Damo et al., 2013; Diaz-Ochoa et al., 2016; Gaddy et al., 2014; Haley et al., 2015; Hood et al., 2012; Liu et al., 2012), its involvement against several human pathogens, including group A streptococcus (GAS), is poorly understood. GAS is a versatile human-specific pathogen that colonizes different anatomic sites and causes diverse disease manifestations (Carapetis et al., 2005; Cunningham, 2000; Olsen et al., 2009). Furthermore, recurring and untreated infections can lead to post-infection immune-mediated complications such as rheumatic heart disease and post-streptococcal glomerulonephritis (Carapetis et al., 2016; Maurice, 2013; Rodriguez-Iturbe and Batsford, 2007). Given the morbidity and mortality associated with GAS infections, and the lack of clinically available prophylactic measures, identification of novel vaccine or antimicrobial targets to treat GAS infections is imperative (Carapetis et al., 2005; Carapetis et al., 2016; Sheel et al., 2016; Steer et al., 2016, 2013).