Without biopsy
Fluorescent urine will allow doctors to find out how the transplant is doing
Maxim Abdulaev, "The Attic"
Scientists from the Georgia Institute of Technology have figured out how to notice the rejection of a transplanted organ without a biopsy – a painful, traumatic and not always accurate method. The new method can detect the aggression of the immune system against the transplant in time and begin treatment with immunosuppressants. It uses iron oxide nanoparticles and glowing probes that enter the urine only if the immune system attacks foreign cells.
The immune system does not always put up with transplantation and can attack transplanted organs without recognizing them as native. Special white blood cells, T-killers, detecting an alien, inject granzymes into it – proteins that trigger apoptosis, that is, cell death. Granzymes belong to a class of proteins that are able to break down other proteins. It is the T-killers that destroy the cells of implanted organs with the help of granzymes.
The authors of the article Mac et al. Non-invasive early detection of acute transplant rejection via nanosensors of granzyme B activity, published in the journal Nature Biomedical Engineering, used the ability of granzymes to cut proteins in order to determine whether the immune system has begun to reject transplanted organs. Scientists took iron oxide nanoparticles (IONP, iron oxide nanoparticles) and coated them with peptides, that is, small chains of amino acids. Scientists have collected these sites from sequences of amino acids that cut granzymes, and at the ends of the peptides there is a fluorescent probe that glows in the infrared spectrum.
Figure from an article in Nature Biomedical Engineering – VM.
If the T-killers identify the graft as alien, they will start attacking it with granzymes. Granzymes do not disassemble targets and cut everything that has foreign amino acid sequences. Accordingly, they will cut the peptides of the probes, and those, having come off, will get into the kidneys with the blood flow, where they will filter out and get into the urine. Urine with probes will glow in the infrared spectrum – thus, by looking at it, doctors will be able to understand that the immune system is hostile to transplantation, and take appropriate measures.
An illustration of how a T-killer (dark purple) attacks a graft cell (dark red) with granzymes (gray). They also attack "beacons" (light red) with probes (green). Georgia Tech, Urine Test Detects Organ Transplant Rejection, Could Replace Needle Biopsies.
If the transplants do not arouse suspicion among T-killers, then the urine will not glow, since whole "beacons" will not get into it – their diameter, 47 nanometers, will not allow them to pass through the filter in the kidneys (5 nanometers).
Scientists conducted an experiment on mice – one group was transplanted skin patches from twins (i.e., almost native organs), and the second simply from other individuals – and a single dose of nanoparticles with equipment from peptides and probes was injected into the blood. After the transplant operation, the scientists measured the luminosity of mouse urine every two days and saw that in those who underwent transplantation from another individual, it became brighter with each measurement, while the luminosity of urine in those who received new skin from a twin did not change. After seven days, the brightness of the urine was almost twice as different.
The researchers write that their method will more quickly and accurately detect the rejection of the transplanted organ by the body and will allow the treatment with immunosuppressants to begin sooner, which will prevent T-killers from killing the transplanted organs. And since the method is non–invasive, it surpasses biopsy - a painful procedure associated with the risk of internal bleeding and damage to the transplanted organ.
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