Amazing Immunology!

I am still reviewing all my notes from the American Transplant Congress that occurred last May in sunny San Diego but I wanted to share with you a couple of interesting findings that I learned:

First of all, the importance of alloantibodies in chronic rejection is becoming even more evident. C4d staining has emerged in multiple studies presented as an insensitive marker of this lesion on allografts. However, we still don’t have any better marker. Some promising results came from analyzing gene expression for endothelial markers of activation by the group from Dr Halloran (Canada). Further validation of these findings are still ongoing, including the evaluation if other lesions not related to alloantibodies could also upregulate those genes.

Second, agents that could potentially block the alloantibody toxicity to the endothelium are now being studied in phase II clinical trials. A great drug seems to be Eculizumab that was shown to decrease acute humoral rejection without affecting donor specific antibody levels by blocking the final step of activation of the complement pathway.

Third, among the 3 forms of techniques to detect alloantibody, a positive cytotoxicity assay (CDC) was shown to correlate with worse allograft outcomes compared to more sensitive methods like flow cytometry and luminex, reinforcing the importance of the old-fashion test.

Lastly, the importance of memory T cells in long-term allograft survival is emerging. These T cells have very interesting properties: they have a higher efficiency in mounting a response, do not need any costimulation and have a lower threshold for activation. Some newer agents targeting CD2 and LFA1, dominant markers of memory T cells, have shown some promising data in animal models.

Maybe we should be listen to Einstein now: "Make everything as simple as possible, but not simpler."