Photopheresis for GVHD

This is an interesting immunological intervention that is approved by FDA, but the mechanism of action is not well known. I am surprised many treatments that are routinely used (empirical) but we do not really know why it works. Probably steroids were/are one of those medications which has long history without knowing the mechanism of action.

Extracorporeal photopheresis (ECP) is a relatively new technique used to treat immunological disorders and complications, such as cutaneous T-cell lymphoma(CTCL), graft-versus-host disease(GVHD), solid organ transplant, and Crohn disease. GVHD will be discussed mainly as the observation of what happens through ECP is quite interesting.

The procedure consists of: 1) the photopheresis system draws blood from the patient, 2) Blood is separated by centrifugation into its cellular components and plasma, and red blood cells are returned to the patient, 3) white blood cells are treated with 8-methoxypsoralen(8-MOP) and exposed to ultraviolet A(UVA) radiation, and 4) the phtoactivated white blood cells are returned to the patient.

ECP was believed to work due to DNA damage and subsequent lymphocyte apoptosis by 8-MOP in the presence of UVA. Then later, researchers started thinking that it doesn’t really make sense as only 5 to 10 percent of lymphocytes are treated during a cycle of treatment. Additionally, research found that induced production of TNF-alpha by monocyte, and a shift in the profile of cytokine production and the balance of Th1 and Th2 response after treatment. Currently a more plausible theory is that the apoptotic lymphocytes produced during ECP increased their display of tumor associated antigens, dividing monocyte activation and the maturation of dendritic cells. That mediates regulatory T-cell production and results immune tolerance.

One of the biggest advantage of ECP is that it doesn’t cause systemic immunosuppression. In actual practice, the ECP is combined with immunosuppressives anyway, and cautions are needed. However, utilizing ECP are expected to help less invasive and effective therapy to be used in organ/stem cell transplantation for GVHD. Again, it is going to be interesting to see what theory is going to fully explain the phenomenon.

References
Knobler, R., Barr, M., Couriel, D., et al. (2009). Extracorporeal photopheresis: past, present and future. Journal of American Academy of Dermatology, 61(4), 652-665.
Xia, C., Canpbell, K., and Clare-Salzler, M. (2009). Extracorporeal photopheresis-induced immune tolerance: a focus on modulation of antigen-presenting cells and induction of regulatory T cells by apoptotic cells. Current Opinion in Organ Transplantation, 14, 338-343.