Advances in understanding the pathogenesis of graft‐versus‐host disease

Abstract

Allogeneic haematopoietic stem cell transplantation (HCT) is a potent immunotherapy with curative potential for several haematological disorders. Overcoming the immunological barrier of acute graft-versus-host disease (GVHD) remains a fundamental impediment to expanding the efficacy of HCT. GVHD reflects a complex pathological interaction between the innate and adaptive immune systems of the host and donor. Over the past decade there has been a tremendous advancement in our understanding of the cellular and molecular underpinnings of this devastating disease. In this review, we cover several recently appreciated facets of GVHD pathogenesis including novel extracellular mediators of inflammation, immune subsets, intracellular signal transduction, post-translation modifications and epigenetic regulation. We begin to develop general themes regarding the immunological pathways in GVHD pathogenesis, discuss critical outstanding questions, and explore new avenues for GVHD treatment and prevention.

Type 2 innate lymphoid cells treat and prevent acute gastrointestinal graft-versus-host disease

“…However, despite highly potent therapy targeting T cells such as alemtuzumab, outcome for patients with corticosteroid-nonresponsive aGVHD has not improved (7). This has led to increasing interest in the role of other proinflammatory immune cells, such as macrophages, neutrophils, and B lymphocytes, in the pathophysiology of aGVHD, and the local function of antiinflammatory immune and non-immune cells (9,10).…”

Alloreactivity: the Janus-face of hematopoietic stem cell transplantation

“…Graft rejection is always associated with detrimental effects for the patient. [5][6][7][8][9] In contrast, the graft-versus-host reactions present a Janus face. The detrimental part, graft-versus-host disease, remains the most important direct or indirect cause for nonrelapse mortality after allogeneic HSCT.…”

“…The detrimental part, graft-versus-host disease, remains the most important direct or indirect cause for nonrelapse mortality after allogeneic HSCT. 1,[5][6][7] The 'other face', the graft-versus-malignancy effect, is desired and may result in cure of the recipient. 10 HSCT presents also as role model of precision medicine: one individual donor is selected for one individual recipient based on genetic findings.…”

Successful long‐term outcome after combined hematopoietic stem cell transplantation and small bowel transplantation: A case report and review of the literature

“…The success of allogeneic HSCT is limited by GVHD, with rates of clinically significant acute GVHD approximately 40% for recipients from HLA‐matched siblings and even higher for HLA‐matched or mismatched unrelated donors. Less than half of these patients have a demonstrable response after corticosteroid treatment, and for those without an adequate response after high dose steroid therapy, mortality can exceed 90% …”