Graft-versus-host disease
Under the graft-versus- host disease ( GVHD; German: graft - versus-host disease, in English: Graft- versus- host disease ( GvHD ) ) refers to an immunological reaction that occur as a result of allogeneic bone marrow or stem cell can. In the GvHD response mainly contained in the graft T - lymphocytes from a donor to the recipient organism. Most frequently manifest symptoms of GVHD in the skin, the liver, the intestines and the eye. The GVHD is split up into four severity levels on the severity and number of organs involved.
The risk of developing GVHD is closely together with the compatibility that is determined by the human leukocyte antigen ( HLA). However, despite optimal screening approximately 30 to 40% of patients in allogeneic transplantation from HLA-identical sibling donors develop acute GVHD mild to moderate severity; about 10 % suffer a difficult to control GVHD. Although different techniques of preparation of grafts have the risk of GVHD and therapieassoziiertem Frühversterben (early treatment related mortality, TRM) reduced, but did not lead to a measurable increase in the survival rate.
Immunosuppressants such as cyclosporine, corticosteroids, antimetabolites, and monoclonal anti- lymphocyte antibodies are now used routinely to control the GVHD better. Although GVHD is a significant health risk in allogeneic stem cell or bone marrow transplants, can use the receiver also has a moderate form of GVHD, as T - cells of the graft and any remaining tumor cells of the host destroy ( graft-versus- malignancy effect).
Graft- versus- malignancy effect
While it is in the GVHD to an adverse reaction of donor lymphocytes to the host organism, also called " graft versus leukemia " ( GVL ) or more generally " graft-versus- malignancy " (GVM ) is the reaction directed against malignant cells, called, quite desirable. Responsible for this reaction are in particular the CD56 / CD3 -NK - cells of the donor - they are able to lyse tumor cells without specific antigen recognition. The function of NK cells is thereby regulated by a combination of different stimulating and inhibiting cell-cell interactions. Lately, especially the group of immunoglobulin-like receptors ( KIR ) has moved into the scientific interest. These surface receptors expressed by NK cells and recognize epitopes that are typical for the MHC - I complex.
As ligands for inhibitory KIR receptors are mainly the HLA -C molecules, which can be found on many cells of the body. The KIR -HLA interaction is subject to a high genetic polymorphism. The HLA-C compatibility is under this aspect for hematopoietic stem cell transplantation of importance - are cells of the recipient will not be able to express the matching KIR - ligand, these cells are the goal of leading to inevitable cell death NK cell action.
In theory, this incompatibility should therefore, in addition to the desired effects of the GVL response, also contribute to a generalized occurrence of GVHD; Paradoxically, this is not the case. As Italian doctors were able to show the incompatibility of KIR ligands indeed was at a family - allogeneic stem cell transplantation is actually related to the occurrence of alloreactive NK cells, which could not be blocked by the MHC - I complex of the recipient cells - such a constellation but resulted in a reduced rate of relapse in AML high-risk patients, without the risk of GVHD or graft failure increase significantly.
Similar conclusions arrived Polish researchers in the study of 130 patients who had received an allogeneic stem cell transplantation from unrelated donors. German researchers were able to identify the HLA -C characteristics of the receiver as an important prognostic factor in this context, in a retrospective examination of 220 stem cell transplants between HLA-matched twins in myeloid and lymphoid disorders.
Swell
- Immunology
- Transplantation medicine