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Allograft vascular disease: comparison of heart and other grafted organs
1Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, USA.
Insights
Allograft vasculopathy, a vascular disease in transplanted organs, shares similarities across different transplants. This condition involves intimal thickening and immune cell infiltration, impacting graft survival and monitoring strategies.
Area of Science:
- Transplantation immunology
- Vascular pathology
- Graft rejection
Background:
- Allograft vasculopathy (AV) is a significant complication following organ transplantation.
- It is characterized by diffuse intimal thickening and inflammatory infiltrates in graft vasculature.
- AV shares pathological features across various solid organ transplants, including heart, liver, pancreas, and kidney.
Purpose of the Study:
- To investigate the similarities and differences in vasculopathy across various allografts.
- To understand the cellular and matrix components of intimal thickening in AV.
- To assess the potential for monitoring AV in different transplant types.
Main Methods:
- Histopathological examination of allograft tissues from heart, liver, pancreas, and kidney.
- Analysis of intimal and medial changes, including smooth muscle cell proliferation, matrix deposition, and inflammatory cell infiltration.
- Comparison of vascular changes in different allograft types and at various time points post-transplant.
Main Results:
- A consistent pattern of intimal thickening, smooth muscle cell proliferation within a lipid- and glycosaminoglycan-rich matrix, and T cell/macrophage infiltration was observed in most allografts.
- Similar vascular changes were noted in heart, liver, pancreas, and kidney allografts.
- Lung allografts showed architecturally similar but less severe vascular changes, with obliterative bronchiolitis being the primary manifestation of chronic rejection.
- Eccentric lesions, resembling native atherosclerosis, were noted in heart allografts, potentially indicating pre-existing donor disease.
Conclusions:
- Allograft vasculopathy exhibits a common pathological pattern across diverse solid organ transplants.
- The presence of AV in heart allografts may be complicated by underlying donor atherosclerosis.
- Detection of vascular changes in renal and pancreas biopsies may offer a method for monitoring therapeutic interventions.
Abstract:
A striking resemblance exists between the vasculopathy in several different allografts. The arteriopathy of epicardial coronary arteries is diffuse, involving proximal, distal, and small branch segments in a generally concentric pattern of intimal thickening. Smooth muscle cells in a lipid- and glycosaminoglycan-rich matrix are the predominant components of this expanded intima. Varying amounts of collagen are present, more being present late posttransplant. A superficial and, to a lesser degree, deep, bandlike infiltrate of T cells and macrophages is uniformly present, although it is somewhat more prominent in early lesions as compared to more severely narrowed arteries from longer-term, susceptible grafts. The media is likewise altered by areas of lipid and glycosaminoglycan deposition associated with smooth muscle cell loss and phenotypic modulation. The media is altered in an outside-to-inside direction, with percolation of adventitial leukocytes into the outer media. Virtually all of the coronary features are seen in the medium to large arteries of liver, pancreas, and kidney allografts. Chronic rejection in lung allografts is manifest by obliterative bronchiolitis; vascular changes, although architecturally similar, are somewhat less common and result in less-severe luminal narrowing. The role of allograft vasculopathy in chronic lung rejection is thus less certain. A finding perhaps unique to epicardial coronary arteries of heart allografts is the presence of eccentric lesions more typical of native atherosclerosis. Many of the latter grafts probably have preexistent, undetected donor disease. Sequential evaluation of vascular changes is limited in human biopsy material by their general absence in endomyocardial or core liver needle specimens. Fortunately, vascular changes can be detected in some renal and pancreas core needle biopsies, and these findings may provide an avenue for monitoring the effectiveness of immunosuppressive therapy, antiviral or lipid-altering therapies, or modifications of smooth muscle cell proliferation and glycosaminoglycan deposition yet to be developed.