Detecting Donor-Derived DNA by Real-Time PCR in Recipients Suspected of Graft-Versus-Host-Diseases After Liver Transplantation: A Case Series and Literature Review

Abstract

Background Graft-versus-host disease (GVHD) after liver transplantation (LT) is a rare but fatal complication. GVHD diagnosis is usually based on clinical symptoms and pathologic confirmation. However, it is often misdiagnosed due to its non-specific symptoms. Here, we report the detection of donor-cell chimerism using peripheral blood (PB) donor-derived deoxyribonucleic acid (ddDNA) for 3 cases with suspected GVHD after LT (GVHD-LT) through real-time quantitative polymerase chain reaction (qPCR) assay targeting 39 insertions and/or deletions of chromosomes. Material/Methods The qPCR assay for detecting donor-cell chimerism was performed for 3 post-LT patients with suspected GVHD using KMRtype ® and KMRtrack ® assays (GenDx, Netherlands). The mean recipient/donor-cell fraction of informative markers unique to each recipient or donor was calculated. Results In Case 1, who received living donor LT (LDLT) from his daughter, initial sign was diarrhea at post-operative day (POD) #23. Case 2 received unrelated deceased donor LT and initial sign was cytopenia at POD #29. Case 3 received LDLT from her son and GVHD associated cytopenia was developed at POD #80. Average PB ddDNA fractions in post-transplant samples of cases 1, 2, and 3 were 39.68%, 78.38%, and 4.76%, respectively. Despite an active treatment including steroid and tumor necrosis factor-α inhibitor, 2 patients (cases 1 and 2) died due to multiple organ failures. Conclusions Early detection of donor-cell chimerism may help halt fatal progression of GVHD-LT. A qPCR test targeting INDEL of chromosomes would be a helpful procedure for timely diagnosis of GVHD.

Free-Circulating Nucleic Acids as Biomarkers in Patients After Solid Organ Transplantation

“…GvHD occurs due to recognition of host antigens as foreign by immunocompetent T cells in the graft, followed by extensive tissue damage and life-threatening complications. A pilot study by Ha et al [ 23 ] showed the promising role of early detection of donor cell chimerism using peripheral blood donor-derived DNA through real-time PCR reaction targeting 39 insertion and/or deletions of chromosomes to halt fatal progression of GvHD after liver grafting.…”