Yesterday, Dr Nishime spoke to the Kaiser transplant support group about a new blood test that will replace the need for a heart biopsy to determine rejection. The test is called Allomap and was developed by Xdx, Inc. of Brisbane CA. The science behind it is quite interesting.
When the body begins to actively reject the heart, the process begins in the cellular immune system. These white cells activate by switching on genes that make specific proteins. These proteins then direct the cells to begin their killer and rejection behavior. Currently, the only way to observe this is to look at the end result, after the damage is done. This is diagnosed with a heart biopsy. Under the microscope, infiltration of the white cells into the heart muscle indicates the degree of rejection. Allomap is like gathering intelligence on the ground forces amassing prior to the attack.
What Allomap does is to measure the activation of the genes that start this process. When a gene is activated, the first step is to make a RNA copy of that gene from our DNA. The RNA is then transcribed and produces the desired protein. Allomap measures the level of the RNA reflecting the gene activity in that cell.
All that is needed is a small sample of blood. That's the easy part. There are only minute amounts of RNA in the sample, truly insufficient to measure directly. In order to have enough RNA to measure, millions of copies must be made first. The problem is, RNA is very fragile. It would be like copying wet tissue paper by sending it through a document feeder. It would shred on the first pass. To make copies, a stronger molecule is needed, so the RNA is first converted (translated) into DNA. In the conversion and copying process, short sequences of DNA specific to the genes being studied are used to bracket and copy only a cropped version of the gene; in the same way you would crop a photograph before printing it.
Then the copier is turned on and left running. The production is exponential, eventually making millions of copies of the turned-on gene. Now it can be measured. The process is called PCR, (Polymerase Chain Reaction). Allomap measure 11 genes of interest and 9 control genes.
At this point, the amount of data generated is huge, too much to be useful for interpretation. This is where the big computers come in. Since the process is proprietary, I can only imagine that some complex algorhythm using a type of artificial intelligence distills all of the data down to a single number, not unlike how an actuary works. They give you the bottom line.
In studies comparing Allomap to the 'Gold Standard' heart biopsy, the correlation is amazingly good, better than 99% Sensitivity. This means that it misses rejection in less than 10 out of 1000 cases.
Once again, I find myself very fortunate in that this new lab test was FDA approved for clinical use one week after I had my heart transplant, allowing me to be part of the first group to benefit from it. Instead of having 13 heart biopsies this year, I will only have eight
Life is good.