Chapter 29
Transplantation immunology: Solid organ and bone marrow

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Development of the field of organ and tissue transplantation has accelerated remarkably since the human MHC was discovered in 1967. Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. The roles of the different components of the immune system involved in the tolerance or rejection of grafts and in graft-versus-host disease have been clarified. These components include antibodies, antigen-presenting cells, helper and cytotoxic T-cell subsets, immune cell-surface molecules, signaling mechanisms, and cytokines. The development of pharmacologic and biological agents that interfere with the alloimmune response has had a crucial role in the success of organ transplantation. Combinations of these agents work synergistically, leading to lower doses of immunosuppressive drugs and reduced toxicity. Reports of significant numbers of successful solid-organ transplantations include those of the kidneys, liver, heart, and lung. The use of bone marrow transplantation for hematologic diseases, particularly hematologic malignancies and primary immunodeficiencies, has become the treatment of choice in many of these conditions. Other sources of hematopoietic stem cells are also being used, and diverse immunosuppressive drug regimens of reduced intensity are being proposed to circumvent the mortality associated with the toxicity of these drugs. Gene therapy to correct inherited diseases by means of infusion of gene-modified autologous hematopoietic stem cells has shown efficacy in 2 forms of severe combined immunodeficiency, providing an alternative to allogeneic tissue transplantation.

Section snippets

MHC

Histocompatibility antigens are tissue cell-surface antigens capable of inducing an immune response in a genetically dissimilar (allogeneic) recipient, resulting in the rejection of the tissues or cells bearing those antigens. The genes that encode these antigens reside in the MHC region on the short arm of human chromosome 6 (Fig 1). The HLA complex contains more than 200 genes, more than 40 of which encode leukocyte antigens.2, 3 These genes and their encoded cell-surface and soluble protein

Role of alloimmune antibodies

The strongest evidence for a role for antibodies in graft rejection is the hyperacute rejection of primarily vascularized organs, such as the kidney and heart. High titers of antidonor antibodies can be demonstrated in recipients presenting with these reactions.6 These antibodies combine with HLA antigens on endothelial cells, with subsequent complement fixation and accumulation of polymorphonuclear cells. Endothelial damage then occurs, probably as a result of enzymes released from

Immunosuppression

More information on immunosuppresion regimens can be found in Table I.

Currently, there is no method that will suppress the host's immune response to antigens of the graft and at the same time maintain other immune responses. Nonspecific immunosuppressive agents are needed to prevent rejection of the transplanted organ, which can occur even though HLA-matched donors are used. The development of immunosuppressive strategies during the past 4 decades reflects enormous progress in understanding the

Solid-organ transplantation

The explosive growth of transplantation since the discovery of HLA in 1967 is attested to by the fact that, according to the Global Database on Donation and Transplantation gathering data from 97 countries, in 2007 around 100,000 solid-organ transplantations were performed per year worldwide: 68,250 are kidney transplantations (45% from living donors), 19,850 are liver transplantations (14% from living donors), 5,179 are heart transplantations, 3,245 are lung transplantations, and 2,797 are

Bone marrow transplantation

Since 1955, more than 240,000 bone marrow transplantations have been performed worldwide at 450 centers in 47 countries for the treatment of more than 50 different fatal diseases (Table III).42 Most of these transplantations have been done by reinfusing stored autologous marrow cells collected before the patient receives intensive chemotherapy or irradiation. Annually, 25,000 to 35,000 autologous transplantations are performed compared with approximately 15,000 allogeneic transplantations.

Conclusions

Advances in transplantation immunology have allowed the exponential growth of organ and tissue transplantation in medicine over the last 3 decades. Newer immunosuppressive agents have allowed the control of solid-organ and tissue rejection and GVHD, even when HLA incompatibility is present. For the treatment of hematologic disorders, including primary immunodeficiencies, hematopoietic stem cell transplantation is not only feasible but is also the treatment of choice in many cases. Future

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    Disclosure of potential conflict of interest: J. Chinen has declared that he has no conflict of interest. R. H. Buckley has received research support from the National Institute of Allergy and Infectious Diseases and is the Chair of the Medical Advisory Committee for the Immune Deficiency Foundation.

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