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PNAS study reveals why organs fail following massive trauma

ins that play a central role in T-cell mediated immune and organ failure. Given that severe trauma effects as many as 20 percent of the 20,000 or so human genes, finding the genes and proteins involved in T cell anergy and apoptosis amid this storm has been a challenge.

Researchers took blood samples from 22 healthy subjects, and from 18 consenting patients who had experienced severe trauma, and were in the midst of organ failure. The team then used unique, clinically applicable techniques to separate out each immune cell type in the patients' blood into pure samples for study. Only when researchers compared pure samples of the same immune cell types (e.g. T cells to T cells) did meaningful patterns emerge. The authors achieved a statistically significant picture of the differences between traumatized and healthy patients for the first time, and despite skeptics that said it could not be done.

With pure samples in hand, researchers used microarray technology to generate a long list of genes that change when a person undergoes massive trauma. They then ran that list through a database of genetic information to see which of the genes changed by trauma were listed in the literature as having a role in T cell function. What emerged was a map of the likely functions of hundreds of genes and proteins related to T cell post-trauma dysfunction, and their likely partners in signaling pathways. The final step was to demonstrate that the proteins associated with those genes have an actual role in organ failure via real-world biochemical tests.

Results showed that the expression of nearly 5,700 genes related to T cell function is changed in cases of massive trauma, as are 2800 genes related to the function of macrophages, partnering immune cells necessary to T cell activation. Trauma had the most profound effect on just 338 of the genes, an at least two-fold change in their expression, the process by which the information they store is converted into
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Source:University of Rochester Medical Center


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