Stem cell treatment for lupus

Systemic Lupus Erythematosus (SLE or lupus) is a devastating autoimmune disease. It primarily affects women of childbearing age and can cause irreversible damage to the kidneys and other organs. Before the advent of modern immunosuppression is was nearly 100% fatal. Even today treatment does not generally cure lupus and increases the risk of severe infections. Some SLE patients do not respond to even high doses of immunosuppression.

Presumably, the underlying "cause" of SLE is immune cells that have become dysregulated, allowing them to recognize self-antigens (that is proteins and other molecules produced by the patient's own body) as dangerous and attack them like they would an infection. This hypothesis is supported by the finiding that SLE patients make antibodies to various self-antigens and that damage to the kidney is mediated by the complement system, which normally acts against bacteria or virally-infected cells

Since SLE generally develops in adolescence or later, it seems that it is due to deviation of the immune system toward self-reactivity. If the immune system could somehow be "reset" it might cure the disease. A new trial, published in JAMA, suggests that a treatment akin to bone marrow transplantation might accomplish this in some patients.

Bone marrow transplantation started as a way to give cancer patients more chemotherapy and radiation. Since these treatments kills off immune cells, it predisposes to infection and if you give too much the immune system might never recover, by giving back immune cells you can give more chemo and radiation. It turns out to be more complicated (more detail is in this previous post) but that's the basic idea.

Doing a transplant for SLE turns that idea on its head. Here the rationale is to kill off immune cells. Hopefully when the immune system is regenerated it will no longer react against normal proteins.

To minimize side effects, the investigators didn't give the patients someone elses bone marrow, but rather gathered the patients own stem cells (which can differentiate into all the different types of immune cells) then treated them with doses of chemotherapy that don't completely eradicate the existing immune system (this is called "non-myeloablatve" whereas "myeloablative" therapy completely destroys the immune system). After this treatment, sten cells are reinfused and, hopefully, a new immune system develops that doesn't cause lupus.

Note, I wouldn't technically describe this treatment as a transplant since cells are collected and reinfused from/into the same patient. A true transplant moved cells from one person to the other.

In the trail, about 1/2 of the patients were "cured" as defined by being alive without needing signficant immunosuppression 5 years later, although lupus did redevelop as late as 5 years later (not all patients have been followed for 5 years, so the cure rate is a stastical measure). Only 1 patient died from complications thought to be related to the transplant and overall survival at 5 years was estimated at 84% which is higher than would have been expected for an untreated group of patinets with severe lupus refractory to standard treatements.

As one of the authors notes in a press release

"Fortunately, the majority of patients with lupus can be successfully managed with our available medical therapies. However, for the very severely ill subset of lupus patients who have failed conventional therapies, stem cell transplantation provides a promising new alternative."