Pathogenesis of steroid refractoriness in acute graft versus host disease

Published Date: 21st October 2026

Publication Authors: Abouzeid. M

Abstract
Allogenic stem cell transplant (SCT) is the only curative option for many haematologic disorders. However, graft versus host disease (GVHD) remains a major limitation. Given its inflammatory nature, systemic steroids are the first line therapy. Nevertheless, steroid refractoriness (SR) is encountered in about 50% of cases and this cohort have dismal outcome. Therefore, understanding steroid actions and potential mechanisms driving SR is of paramount importance to design targeted therapies and improve steroid responsiveness. Steroid actions encompass a cascade of events starting from activation of its canonical receptors GR α then nuclear translocation followed by activation of its response elements (GRE) until its effect at gene transcription level. This cascade includes several steps that are subject to alteration and interruption by a plethora of factors that would potentially induce SR. SR could be congenital or acquired, generalised or tissue specific, complete or just partial. Acquired SR could be related to downregulation of its canonical receptors, impaired nuclear translocation, impaired GRE binding and efficacy, upregulation of its antagonist isoform GR β as well as potential gene transcription alterations and epigenetic effects. In addition to potential non-T cell related mechanisms. Therefore, SR in aGVHD is likely a multifactorial and multi-level phenomenon related to interruption of steroid actions at one or more levels. Here, we attempted to examine potential mechanisms driving SR in aGVHD. This would lay the foundation to overcome SR and improve outcome.

Debes, M; Abouzeid, M et al. (2026). Pathogenesis of steroid refractoriness in acute graft versus host disease. Molecular Biology Reports. 53, Article No. 1769. [Online]. Available at: https://dx.doi.org/10.1007/s11033-026-12935-z [Accessed 29 October 2026]