Sensitive noninvasive marker for the diagnosis of probable bacterial or viral infection

Abstract

Urinary trypsin inhibitor (uTi) is a product of elastase-mediated degradation of interleukin-alpha-inhibitor (I-alpha-I). Its activity increases in the urine of patients with a malignancy, inflammation, or infection, or in late pregnancy. The objective of this study was to compare the sensitivity of uTi in urine with that of serum quantitative C-reactive protein (CRP) for diagnosing infection, as indicated by white cell response and clinical assessment. Ninety controls and 171 patients with various systemic infections were enrolled. We measured uTi enzymatically on a Cobas Fara (Roche Diagnostics). Patients were separated into bacterial, probable bacterial, viral, or probable viral groups based on the results of a complete blood count with differential (CBC), urinalysis (UA), and clinical assessment. In the bacterial (n=70) and control (n=90) groups, the uTi values (mean+/-SE) were 25.3+/-3.1 mg/L and 2.8+/-0.8 mg/L, respectively. uTi (at 2.7 mg/L) had a diagnostic sensitivity of 91% and specificity of 82% (AUC=0.889), whereas CRP (at a cutoff of 10 mg/L) had a sensitivity and specificity of 82% and 96%, respectively (AUC=0.921). As a marker of infection (positive in both bacterial and viral groups), uTi had a sensitivity of 91% (AUC=0.884) vs. 89% (AUC=0.828) for CRP. Our data indicate that uTi has sufficient clinical sensitivity for screening systemic infections, and may have diagnostic value as a noninvasive test.

Development of a method for urine bikunin/urinary trypsin inhibitor (UTI) quantitation and structural characterization: Application to type 1 and type 2 diabetes

“…No correlation between age and UTI levels within each tested group was found. Quantitative data obtained for healthy controls were in agreement with reference values reported in literature . Among patients, three presented with microalbuminuria that represents an early sign of renal impairment.…”

“…Free bikunin is rapidly cleared from circulation by both tissue uptake and renal excretion and it is found in urine as the urinary trypsin inhibitor (UTI). UTI levels are usually low in healthy individuals but they increase up to tenfold in both acute and chronic inflammatory diseases . According to a plethora of papers, bikunin can be considered a positive acute phase protein .…”

Utilization of Electronic Health Records for the Assessment of Adiponectin Receptor Autoantibodies during the Progression of Cardio-metabolic Comorbidities

“…The levels of uristatin that is formed as part of the anti-inflammatory response (38) did not predict disease progression. Uristatin immunoassay values are <7.5 mg/mL in ~98% of patients in the absence of infection, inflammation, or kidney disease (38)(39)(40), however, we found that significant infection or inflammation was common in diabetes patients (22%) but unable to be assessed in the CVAD cohort due to absence of samples. This lack of correlation between inflammation and the development of comorbidities is unsurprising because a single incidence of inflammation may be quickly resolved is not expected to affect the long-term outcomes.…”

“…Uristatin immunoassay values ranged from 0.1 to 278.9 mg/L, with 81% of the patients within the normal range <7.5 mg/mL at sample collection ( Table 3). The 98% reference range of <7.5 mg/mL for normal results was previously determined for 6292 patients lacking infection, inflammation or kidney disease (37)(38)(39)(40). In these samples, 19% (n=127) contained uristatin ³7.5 mg/L.…”

Emergence of single-molecule sequencing and potential for molecular diagnostic applications

“…At present, the field of pathogen and microbial diagnostics utilizes both immunoassay-based measurements as well as nucleic acid-based methods, the latter of which are rapidly growing in utility. Immunoassays can examine the presence of an immune response in an individual or they can detect antigens produced directly by the pathogen; however, they often lack the sensitivity required for definitive diagnosis, particularly in early stages of an infection, often making therapy choices difficult [35]. Early utilization of nucleic acid measurements has focused on PCR-based amplification to allow enrichment of the pathogen genome signal in regions of pre-defined interest and initially focused on viral sequences [36,37], with newer emphasis turning to microbial or viral arrays, which allow the interrogation of selected species that can be difficult to culture and are of biomedical importance [38].…”