A 15-year-old male develops severe cardiomyopathy after contracting an infective myocarditis from the Coxsackie virus, leading to his placement on the cardiac transplant list. Two weeks post-transplantation from a matched donor, he experiences dyspnea upon exertion. Extensive evaluation, including cardiac catheterization and endomyocardial biopsy, is conducted. Which of the following findings best indicates acute graft rejection?
A. Concentric coronary atherosclerosis
B. Dense interstitial lymphocytic infiltrate
C. Perivascular infiltrate with abundant eosinophils
D. Patchy necrosis with granulation tissue
E. Scant inflammatory cells and interstitial fibrosis
The most indicative finding of acute graft rejection in this scenario is:
B. Dense interstitial lymphocytic infiltrate
The patient described in the question stem exhibits symptoms consistent with acute rejection of his cardiac transplant. Acute rejection typically occurs within one to four weeks post-transplant and predominantly involves the cell-mediated pathway. Although rare, humoral rejection, characterized by anti-donor host antibodies, can also occur, diagnosed through direct immunofluorescence. The patient’s symptom onset two weeks post-transplant aligns with the timeframe for acute rejection.
Histopathologically, acute rejection is characterized by a dense infiltrate of mononuclear cells, primarily T-lymphocytes, observed in endomyocardial biopsy. This rejection mechanism involves host T-lymphocyte sensitization against graft MHC antigens. Surveillance typically allows for the diagnosis of rejection before symptom onset, but progressive rejection can manifest with symptoms akin to heart failure, such as dyspnea on exertion or paroxysmal nocturnal dyspnea.
(Choice A) Concentric coronary atherosclerosis detected on angiography is not indicative of rejection. In transplant patients, the presence of atherosclerosis on angiography suggests preexisting conditions in the donor heart before organ procurement.
(Choice C) A perivascular infiltrate with abundant eosinophils aligns with the histopathological profile of hypersensitivity myocarditis. This condition often arises from the initiation of new drug therapies, triggering an allergic response in the body.
(Choice D) Patchy necrosis with granulation tissue indicates ischemic injury to the donor heart. Ischemia in the donor heart can occur during various phases, such as during resuscitation attempts, organ transportation, or initial perfusion post-transplantation. Atherosclerosis in the donor heart may also contribute to ischemic episodes.
(Choice E) Scant inflammatory cells and interstitial fibrosis are characteristic of chronic rejection. This process, orchestrated by host T-lymphocytes, B-lymphocytes, and antibodies, typically manifests months to years following solid organ transplantation.
Next
Acute transplant Rejection
- Incidence: Approximately 50% of cases of post-transplant organ dysfunction.
- Onset: Typically within six months post-transplantation, often occurring within weeks to months.
- Risk Factors: Include HLA incompatibility, inadequate immunosuppression, or patient nonadherence.
Pathophysiology
- Acute Cellular Rejection (Type IV Hypersensitivity Reaction):
- Recipient CD4+ T cells react with donor MHC class II antigens, leading to the differentiation into Th1 helper T cells, release of cytokines (e.g., INF-γ), macrophage recruitment, and inflammation of parenchymal and endothelial tissues.
- Recipient CD8+ T cells react with donor MHC class I antigens, causing direct cytotoxic damage to cells.
- Acute Humoral Rejection (Type II Hypersensitivity Reaction):
- Recipient antibodies, either preformed or developed post-transplantation, target donor HLA antigens.
Clinical Features:
- Pain in the graft region, graft edema, fever, and deterioration of the general condition.
Diagnostics:
- Screening: Serial organ function tests to monitor for decline.
- Biopsy (confirmatory):
- Dense interstitial lymphocytic infiltrate with vasculitis.
- Heterogeneous mononuclear aggregates with or without antibody deposition.
- Positive C4d staining indicates humoral graft rejection, while negative staining suggests cellular rejection.
Treatment:
- Acute Cellular Rejection:
- First-line: High-dose glucocorticoids.
- Second-line: Lymphocyte-depleting antibodies or OKT3 (muromonab or anti-T-cell antibody).
- Acute Humoral Rejection:
- First-line: Plasmapheresis, IVIG, anti-CD20 antibodies, and lymphocyte-depleting antibodies.
- Corticosteroids may be used adjunctively.
Prevention:
Preoperative crossmatching and ABO grouping, preoperative HLA matching, and post-transplant immunosuppressive therapy.