Use of Short Tandem Repeats for DNA Fingerprinting to Rapidly Diagnose Graft-versus-Host Disease in Solid Organ Transplant Patients

Abstract

Background. Graft-versus-host disease (GVHD) is a rare complication following liver transplantation and carries a poor prognosis with mortality approaching 90 -95%. Diagnosis of GVHD is often delayed due to early symptoms mimicking more common, entities such as drug reactions and viral syndromes. To date, definitive diagnosis has been difficult and has relied on a constellation of clinical and histopathologic variables. We present the use of short tandem repeat DNA "fingerprinting" technology as a method of early, definitive diagnosis of GVHD in patients after liver transplantation. Methods. A patient status-postorthotopic cadaveric-liver transplant, with an uncomplicated immediate posttransplant course, presented 4 weeks after transplant with fever, diarrhea, and maculopapular rash on her palms, soles, and back. The patient's condition worsened despite empiric treatment for an infectious etiology. Skin and rectal biopsies were suspicious for GVHD. Results. DNA was isolated from the skin and rectal biopsies as well as from a donor lymph node. PCR amplification was done for nine highly polymorphic short tandem repeats for each specimen and a unique DNA "fingerprint" was obtained from each. DNA from skin and rectum demonstrated mixed chimerism with both donor and recipient alleles detected. Thorough analysis confirmed GVHD. Conclusion. Short tandem repeats for DNA fingerprinting represents an efficient and reproducible method for the definitive diagnosis of GVHD after liver transplantation. Rapid detection of GVHD using this technology, coupled with early initiation of therapy, may lead to improved survival for patients with GVHD after solid organ transplant.

Graft-Versus-Host Disease After Simultaneous Pancreas–Kidney Transplantation: A Case Report and Review of the Literature

“…In our case, the skin biopsy FISH showed a Y chromosome in 28% of cells, confirming GVHD. STR analysis of peripheral blood can be helpful for diagnosis and monitoring clinical response to treatment (19). As many of these patients are profoundly lymphopenic, the key for reliable STR testing is to perform enrichment for CD3þ cells.…”

Avoiding Pitfalls: What an Endoscopist Should Know in Liver Transplantation—Part II

“…Chimerism of 3% has been reported in peripheral blood of normal posttransplant patients, while at the same time a number of cases of GVHD lacked chimerism [210,212]. A newly described diagnostic technique, more sensitive than chimerism, consists of application of short tandem repeat assay to detect donor DNA from the affected specimen [213]. Endoscopic features in case of GIT involvement include presence of widespread ulceration extending anywhere from rectum to small intestine.…”

“…Mesenchymal and autologous stem cell transfusion has proved effective in GVHD after bone marrow transplantation and may have a future role in liver transplant recipients [213,216].…”

Treatment of Liver Transplant Graft-Versus-Host Disease With Antibodies Against Tumor Necrosis Factor-α

“…Although high-dose corticosteroids may be the firstline therapy for acute GVHD after stem cell transplant, exclusive corticosteroid therapy or an increase in immunosuppression ar ineffective long-term therapies in adults with GVHD after liver transplant. 2,5,10 Another method includes antilymphocytic agents such as antithymocyte globulin, antilymphocyte globulin, and monoclonal antilymphocyte agents; although this is an improvement over corticosteroids, survival remains poor. 2,5,6,8 Anti-interleukin-2 receptor antibodies have been used successfully in the treatment of GVHD after liver transplant.…”