Corticosteroid resistance is predetermined by early immune response dynamics at acute graft-versus-host disease onset
Sophie Le Grand, Yannick Marie, Delphine Bouteiller, Margo Fernandez, Gwendolyn Marguerit, Marion Lambert, Émeline Mundwiller, Émilie Robert, Régis Peffault de Latour, Gérard Socié, Nicolas Vallet, and David Michonneau
Patients who receive hematopoietic stem cell transplants are at risk of developing graft-versus-host disease (GVHD), where the immune cells descended from the transplanted stem cells attack the transplant recipient’s own tissues. Acute GVHD (aGVHD) is often treated with corticosteroids, but some patients do not respond to treatment. Here, Le Grand et al. demonstrate that this corticosteroid resistance seems to be set at the time of aGVHD development. The authors evaluated peripheral blood samples from two different cohorts and found that those who went on to develop steroid-resistant aGVHD harbored immune cells especially capable of tumor necrosis factor–α (TNF-α) signaling. Their T cells also exhibited the ability to directly transition from a naïve state to a highly activated one, rather than a slow transition observed in those whose disease was steroid sensitive. Together, these data suggest that steroid resistance could be identified at aGVHD onset through analysis of peripheral blood, offering an opportunity for personalized medicine for patients with aGVHD.