Zapping Wayward Cells: Therapy sheds light on transplant complication

Doctors sometimes recommend ultraviolet (UV) light exposure for people suffering from complications of a bone marrow transplant from a donor. The radiation can ameliorate skin lesions, such as rashes and ulcers, that are a common side effect of the procedure. But UV radiation isn’t a standard treatment, in part because its mechanism of action is unknown and no large-scale study has established its effectiveness.

An experiment in which mice received marrow transplants now suggests that UV light wipes out troublemaking immune cells of the skin. Earlier research had suggested that these Langerhans cells react with immune cells derived from the transplant and cause graft-versus-host disease (GVHD), a dangerous complication in which donor immune cells attack the skin, liver, and gut. In the mouse experiment, by hematologist Miriam Merad of the Mount Sinai School of Medicine in New York and her colleagues at several institutions, UV-light exposure before the transplantation prevented GVHD.

The findings could spur formal trials of UV therapy in marrow-transplant patients, says Georgia B. Vogelsang, a transplant physician at Johns Hopkins Medical Institutions in Baltimore.

People typically get bone marrow transplants to fight blood cancers, such as leukemia or lymphoma. First, physicians use chemotherapy and sometimes gamma or X-ray radiation to kill off fast-dividing cells, such as blood stem cells and bone marrow cells, which are the source of both healthy and cancerous blood cells. This treatment wipes out most of the cancer but also eliminates nearly all of the patient’s immune system.

The patient then receives a donor’s healthy marrow cells, which grow into blood cells and reconstitute the immune system.

Langerhans cells, however, are impervious to chemotherapy and gamma and X-ray radiation, says Merad. So, they linger in the patient and often rev up the reconstituted immune system to harmful effect.

In a healthy person, Langerhans cells and white blood cells called T cells play a protective role. Langerhans cells snag invaders and present them to T cells, which sort out harmless substances from threatening ones.

After a marrow transplant, however, holdover Langerhans cells can shift transplant-derived T cells into overdrive, causing inflammation and GVHD reactions, such as skin lesions.

Some test-tube studies had hinted that Langerhans cells are susceptible to UV radiation. In the recent experiments with the mice, UV radiation left few holdover Langerhans cells to react with T cells. However, in mice that weren’t exposed to UV light before bone marrow transplantation, Langerhans cells triggered severe skin lesions, Merad and her colleagues report in the May Nature Medicine.

GVHD is the most common complication of marrow transplants, affecting 30 to 60 percent of recipients, says Kenneth R. Cooke, a transplant physician at the University of Michigan Medical School in Ann Arbor. This high rate “clearly limits the broader application of marrow transplants,” he says.

Doctors can stifle GVHD with powerful drugs, but those compounds suppress immunity, weakening the patient in the continued fight against cancer, Cooke notes.

If UV light were to succeed in stopping even the skin symptoms of GVHD, he says, it would limit the need for steroids or other immune suppressants.

The new study is “extraordinarily thorough,” says Vogelsang. While the story of how UV light modifies the immune system has yet to be fully told, this research “helps to sort it out,” she says.

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