Case 43

Published on 18/02/2015 by admin

Filed under Allergy and Immunology

Last modified 22/04/2025

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CASE 43

Ms. Bell received cardiac transplantation approximately 6 years earlier for a cardiomyopathy that developed after she received chemotherapy (doxorubicin [Adriamycin]) for breast cancer. She has had routine endomyocardial biopsies each year, the last being 1 year ago. At that time the pathologist read the biopsy as normal, with no signs of rejection. The only change in her anti-rejection therapy over the past 2 years was a reduction in the prednisone dose (now 7.5 mg/day) and replacement of cyclosporine (which she had received for nearly 5 years since the time of transplantation) with tacrolimus. You (her son) were told that the advantage of tacrolimus was a slightly improved toxicity profile. You arrived home for a visit this afternoon to find your mother confused and with a droop on the left side of her face/mouth. You immediately call an ambulance and arrange transport to the local hospital.

QUESTIONS FOR GROUP DISCUSSION

RECOMMENDED APPROACH

Implications/Analysis of Clinical History

Ms. Bell received a cardiac transplant 6 years ago, and all the evidence we are provided with indicates that this was a successful graft in that the yearly endomyocardial biopsies have all been normal. In fact, the only change in her anti-rejection therapy has been a reduction in immunosuppressive therapy and change from cyclosporine to tacrolimus, which is slightly less toxic.

ETIOLOGY: TRANSPLANTATION COMPLICATIONS

Graft rejection, infections, malignancies, and drug toxicity are all possible complications after transplantation and immunosuppressive therapy

Graft Rejection

For the most part, grafts are allografts. That is, they are donated from another person who is genetically dissimilar. The rejection of an allograft reflects a composite of both antigen-specific and antigen-nonspecific inflammatory processes that include activation of (1) the intrinsic coagulation pathway; (2) T cells and B cells; and (3) macrophages, neutrophils, mast cells/ basophils, and the vascular endothelium. Cytokines, chemokines, and inflammatory products secreted by antigen-specific and antigen-nonspecific cells all contribute to graft rejection.

Acute Rejection

Acute rejection is a function of, among other things, the degree of MHC incompatibility between donor and host and is minimized both by “matching” of donor and recipient at the MHC before engraftment and by judicious use of immunosuppressive drug therapy after engraftment to decrease the likelihood of sensitization. Despite immunosuppressive therapy, some degree of cell activation can (and generally does) occur, marked both by development of killer CD8+ T cells (CTLs) specific for graft antigen/MHC and by activated CD4+ cells, able to release a variety of molecules capable of engaging other elements of the immune recognition process.