For people with severe autoimmune diseases, a major treatment challenge is preventing the immune system from attacking healthy tissues. Although powerful immune-modifying therapies can provide significant benefits, lasting disease control remains difficult for some patients.

Researchers at the University of Miami Miller School of Medicine have proposed a strategy to potentially improve autologous hematopoietic stem cell transplantation (auto-HSCT), a treatment option for selected patients with severe autoimmune diseases. The approach involves adding post-transplant cyclophosphamide (PTCy), a drug used in donor stem cell transplantation, during the critical period of immune system recovery. Led by Robert Levy, Ph.D., professor of microbiology and immunology and ophthalmology, and researcher Dietlinde Wolf, Ph.D., the team uses multiple sclerosis as a model to explore whether this strategy could also benefit patients with other autoimmune disorders.

Autoimmune diseases occur when the immune system mistakenly attacks healthy tissues. Conditions such as multiple sclerosis, lupus, rheumatoid arthritis, and systemic sclerosis can cause long-term disability and often require ongoing treatment. Auto-HSCT aims to reset the immune system by collecting a patient's own blood-forming stem cells, using conditioning therapy to reduce existing immune cells, and returning the stem cells to restore blood cell production and immune function. However, some autoreactive T cells may survive the treatment and contribute to disease relapse as the immune system recovers.

The researchers propose that the early period of immune reconstitution may offer a therapeutic window to target these surviving autoreactive cells. During this phase, immune cell numbers are temporarily low, and surviving T cells begin proliferating to rebuild immune function. Because cyclophosphamide preferentially affects rapidly dividing cells, administering PTCy several days after transplantation may help eliminate autoreactive cells that escape the initial conditioning treatment, potentially achieving a more complete immune reset.

This proposed strategy builds on experience using PTCy after allogeneic stem cell transplantation, where it helps control harmful immune responses associated with graft-versus-host disease. However, its potential benefits in autoimmune disease treatment require further investigation and clinical validation.

Source: https://news.med.miami.edu/stem-cell-transplant-immune-reset-autoimmune-disease/