Benefit of STR-based chimerism analysis to identify TA-GVHD as a cause of death: Utility of various biological specimens

Abstract

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare condition. It can occur after blood transfusion in immune-compromised and occasionally even in immune-competent patients, and is associated with a mortality rate of >90%. The diagnosis of TA-GVHD is often delayed because of its non-specific clinical features. A case of an immune-competent child who developed TA-GVHD is reported here. DNA profiling (short tandem repeat analysis), a technique that has a wide application in forensic medicine, was performed to detect the presence of donor cells in this patient. The findings suggest that more studies are needed with this tool, and the diagnostic potential of using other multiple biological specimens for DNA profiling such as the hair follicle and buccal swab should be evaluated. This is the first case report where the donor's DNA fingerprinting pattern was substantiated from a patient's hair follicle sample. Chimerism was also present in the blood and buccal swab specimens.

Anti-CD3 Antibody Ameliorates Transfusion-Associated Graft-Versus-Host Disease in a Chemotherapy-Based Mouse Model With Busulfan and Fludarabine

“…The risk factors of this disease include the number and immunoreactivity of contaminating lymphocytes in transfusion components. The dominant mechanism of TA-GVHD in immunocompetent and compromised hosts is exposure to viable donor lymphocytes that are responsive against recipients but are not recognized as foreign substances (3,15) . Similar to GVHD, TA-GVHD requires an immunoactive component, difference in MHC between a donor and a recipient, and susceptibility of a patient's immune system to the engraftment of donor lymphocytes.…”

Transfusion‐associated graft‐versus‐host disease reexamined: potential for improved prevention using a universally applied intervention

“…In this situation, the recipient identifies the donor lymphocytes as “self” (and therefore engraftment occurs), but the donor lymphocytes identify a foreign antigen(s) on recipient cells and attack these cells. The degree of HLA antigen matching required for “self‐identification” has not been fully elucidated; many such cases have had full matches at the A and B loci (and often at the DR locus as well), but some cases have been reported with cross‐reacting antigens at these loci . Minor non‐HLA antigens have also been implicated in animal models, adding another risk factor for family members that may share them .…”

“…However, it is possible that cases are occurring but are misdiagnosed (i.e., underrecognized) or are underreported. Some authors report that the diagnosis was not made upon initial clinical presentation but was recognized only after the patient's condition worsened and/or the patient was transferred to a tertiary care medical center . Multiple reviews cite the possibility that cases can be misdiagnosed as drug reactions and/or viral syndromes or sepsis .…”

“…The degree of HLA antigen matching required for "self-identification" has not been fully elucidated; many such cases have had full matches at the A and B loci (and often at the DR locus as well), but some cases have been reported with cross-reacting antigens at these loci. 12,25,26 Minor non-HLA antigens have also been implicated in animal models, adding another risk factor for family members that may share them. 27 Another factor that could affect risk is the likelihood of substantial variation in immune system function even among apparently immunocompetent patients.…”

“…Some authors report that the diagnosis was not made upon initial clinical presentation but was recognized only after the patient's condition worsened and/or the patient was transferred to a tertiary care medical center. 13,24,26 Multiple reviews cite the possibility that cases can be misdiagnosed as drug reactions and/or viral syndromes or sepsis. 28,42 Even when pancytopenia is present, a clinician may invoke a multifactorial explanation (e.g., secondary infection in addition to a drug reaction).…”