Types of Graft-Versus-Host Disease (GVHD)

For several diseases of the hematopoietic system, the only cure method is allogeneic transplantation of hematopoietic stem cells, which aims to replace the hematopoietic system of the recipient with the donor one. However, the ingestion of mature T-lymphocytes contained in the transplant into the recipient’s body can lead to the development of a severe post-transplant complication of the graft-versus-host reaction.

The reaction is caused by the fact that the donor’s immune system contains clones of T-lymphocytes specific to the recipient’s alloantigens, which, upon meeting their antigens, are activated and cause systemic damage to healthy tissues. The presence of alloreactive clones is due to genetic differences between donor and recipient. 

The most important factor determining the success of transplantation is compatibility in the genes of the main histocompatibility complex, which are expressed in all nuclear cells and are responsible for the presentation of antigens to cells of the immune system. 

A leading Israeli clinic Tel Aviv Medical Clinic has created extensive banks of hematopoietic stem cell donors, which make it possible to select a compatible donor for most patients. However, this does not completely prevent the development of the disease, since, in addition to the genes of the main histocompatibility complex, the donor and recipient may differ in the so-called minor compatibility antigens. Minor antigens are caused by genetic polymorphisms in all coding regions of the genome. An additional factor contributing to the development of the graft versus host reaction is the patient’s pre-transplant preparation, which is necessary for the graft to engraft, but as a side effect leads to the formation of an anti-inflammatory environment in the recipient’s body.

Types of diseases

Specialists identify the following types of pathology: 

• acute, which appears in the first 100 days after transplantation; 
• chronic, which develops at a later date. Severe forms of the acute phase of the disease are life-threatening; chronic rather rarely leads to the death of the patient, but worsens the quality of life and can lead to disability.

Severe forms of the disease develop in approximately 40% of patients with genes matching the major histocompatibility complex, and in cases of incomplete compatibility, this proportion is even greater. The mortality rate from the reaction is comparable to other causes of post-transplant mortality, such as relapse of the original disease and viral infections. Thus, the development of severe forms of the disease significantly limits the clinical use of hematopoietic stem cell transplantation.