Methods for measuring ubiquitin carboxy—terminal hydrolase L1 levels in blood
Inventors
Beligere, Gangamani S. • Brennan, Melissa B. • Grieshaber, Jessica • Pacenti, David • Datwyler, Saul A. • Ramp, John M.
Assignees
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Publication Number
US-12123883-B2
Publication Date
2024-10-22
Expiration Date
Abstract
Disclosed herein are improved methods of processing, measuring, and detecting levels of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in blood samples taken from a human subject at time points within about 8 hours (or about 8 hours or less) after obtaining the sample from the subject. UCH-L1 is an early biomarker for traumatic brain injury (TBI), and there is a need for improved methods for assessing UCH-L1 in blood can aid in the diagnosis and evaluation of a human subject who has sustained or may have sustained a head injury.
Core Innovation
The invention describes an improvement of a method of measuring an amount of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in a whole blood sample obtained from a subject. The improvement comprises processing the sample within about 4 hours, about 6 hours, or about 8 hours after the sample is obtained to avoid a rise in UCH-L1 level that results from storage of the sample, and then testing subsequent to the processing to measure the amount of UCH-L1.
Processing comprises separating plasma from blood cells in the sample and/or separating serum from any clots that arise in the sample, followed by performing a test using the plasma or serum that measures the amount of UCH-L1. Alternatively, the improvement includes performing a test on whole blood that measures the amount of UCH-L1, with subsequent testing using plasma or serum where plasma or serum results are obtained from separation.
The disclosure further frames the measurement of UCH-L1 levels as a measure of traumatic brain injury in subjects who have sustained or may have sustained a head injury. By preventing an increase or rise in UCH-L1 levels between obtaining the sample and obtaining a result from an assay, the method supports assessment using reference levels and multi-sample comparison, including differentiation associated with mild versus moderate-to-severe traumatic brain injury.
Claims Coverage
The document provides two independent claims. Both claims focus on preventing or avoiding a storage-related increase or rise in UCH-L1 levels by processing whole blood within about 4 hours, about 6 hours, or about 8 hours, including options for separating plasma/serum or testing whole blood, and subsequent assay of plasma/serum (or assay of whole blood).
Processing within a defined time window to avoid storage-related UCH-L1 rise
Processing a whole blood sample within about 4 hours, about 6 hours, or about 8 hours after the sample is obtained from the subject to avoid a rise in UCH-L1 level that results from storage, thereby avoiding a rise in UCH-L1 level that results from storage of the sample for longer than 8 hours.
Plasma/serum separation and subsequent UCH-L1 testing
Separating plasma from blood cells and/or separating serum from any clots that arise in the sample as part of processing, and subsequently performing a test using the plasma or serum that measures the amount of UCH-L1.
Whole blood testing with plasma/serum assay option
Performing a test on whole blood that measures the amount of UCH-L1 in the sample, and in embodiments where (a) and (b) are performed, performing an assay using the plasma or serum that measures the amount of UCH-L1.
Avoiding or preventing UCH-L1 increase prior to obtaining assay results
Avoiding or preventing an increase or rise in UCH-L1 levels between the period of time a whole blood sample is obtained from a subject and prior to obtaining a result from an assay on the sample, by processing within about 4 hours, about 6 hours, or about 8 hours and thereby avoiding or preventing an increase or rise in UCH-L1 levels that results from storage of the sample for longer than 8 hours.
Across the two independent claims, the main coverage is preventing storage-related increases in measured UCH-L1 by processing within about 4 to 8 hours after collection, with processing including plasma/serum separation and subsequent UCH-L1 measurement, or optionally performing an assay on whole blood with plasma/serum assay where separation is performed.
Stated Advantages
Avoiding a rise in UCH-L1 level that results from storage of the sample for longer than 8 hours.
Avoiding or preventing an increase or rise in UCH-L1 levels between obtaining the whole blood sample and obtaining a result from an assay.
Documented Applications
Assessing UCH-L1 amount in a subject’s sample as a measure of traumatic brain injury in subjects who have sustained or may have sustained a head injury.
Supporting evaluation associated with mild versus moderate-to-severe traumatic brain injury.
Supporting decision support using CT scan and monitoring progression using reference levels and multi-sample comparison.
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