Donor type microchimerism is an infrequent event following liver transplantation and is not associated with graft acceptance

✍ Scribed by S Norris; M Lawler; S McCann; J Hegarty; C O'Farrelly

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 298 KB
• Volume: 26
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510260407

✦ Synopsis

Donor-type microchimerism, the presence of a minority

However, consensus has not emerged regarding the necessity for donor cells to remain in circulation or tissues distal population of donor-derived haematopoietic cells following solid organ transplantation, has been postulated as a mecha-to the transplanted organ before tolerance can emerge, and the biological relevance of donor microchimerism in allograft nism for induction of donor-specific graft tolerance. The stability, frequency, and relevance of microchimerism with re-recipients remains controversial. 9,10 This has been further complicated by case reports documenting donor microchi-spect to long-term outcome, however, remains uncertain. Using a polymerase chain reaction (PCR)-based method of merism in association with graft rejection. 11 Further studies have failed to document donor microchimerism following microsatellite analysis of highly polymorphic short tandem repeat sequences (STRs) to detect donor-type cells, DNA from orthotopic liver transplantation (OLT) despite infusion of donor bone marrow. 12 As a result, the biological significance 11 patients was analyzed prospectively at specific time points for 12 months following liver transplantation, and from a of donor microchimerism in allograft recipients has been questioned. Much of the published data has depended on further six patients retrospectively 2 years after liver transplantation. Using a panel of STRs, transient peripheral blood the use of highly sensitive polymerase chain reaction (PCR)based technologies to detect donor cells following liver trans-donor microchimerism was detected in 2 of 11 patients at a single time-point following transplantation, but persistent plantation, in particular, nested PCR, which can detect donor or foreign cell populations to a level of one cell in 10 5 -10 6 evidence of donor-derived cells was not observed during the study period. Analysis of DNA extracted from skin and duode-cells. The clinical significance of a detection rate at this level is unclear. num in two patients likewise failed to show donor-type cells at these sites. None of the six patients in the retrospective Hematopoietic chimerism is the term originally used to describe the characteristics of cellular repopulation of the arm showed donor microchimerism, resulting in an overall detection rate of 1.58%. These results suggest that donor host bone marrow cavity with hematopoietic stem cells during allogeneic stem cell transplantation (SCT) following mar-microchimerism following liver transplantation is an infrequent event, and that the generation of graft tolerance is inde-row ablative chemotherapy. We have previously developed a PCR-based strategy to evaluate bone marrow repopulation pendent of microchimerism. (HEPATOLOGY 1997;26:848-852.)

following allogeneic SC. 13 Donor and recipient cells are distinguished by using PCR of short tandem repeats (STR-PCR). Transplantation tolerance, the long-term acceptance of STRs are di-, tri-, or tetra-nucleotide repeat sequences that grafted tissue in the absence of continuous immunosuppresare spread randomly throughout the human genome. Polysion, remains an elusive ideal goal in human transplantation. morphic variation is shown by differences in the number of Proposed mechanisms influencing graft acceptance include repeat sequences between individuals. Thus, STR-PCR can peripheral anergy, clonal deletion of donor-reactive cytotoxic be used to distinguish donor, mixed, or recipient chimerism T cells, and suppression of alloreactive clonotype. 1,2 In recent following allogeneic SCT. In the current study, this approach years, reports of minor percentages of donor-derived denwas used to determine the emergence, stability, and clinical dritic or hematopoietic cells detected in various tissues in relevance of donor microchimerism prospectively in a serial long-term kidney, 3 liver, 4 and heart recipient, 5 referred to as fashion following liver transplantation, and retrospectively ''donor microchimerism'' resulted in a novel theory to eluciin a second group of patients who had undergone transdate the generation of graft tolerance following transplantaplantation two years previously. tion. Many studies have reported donor microchimerism

PATIENTS AND METHODS

years following solid organ transplantation and have highlighted the importance of longlived donor-derived cells in Patients. Eleven patients were enrolled in the study for 12 months generating long-term graft acceptance. [6][7][8] from the time of liver transplantation and followed prospectively, while six patients were studied at 2 years following OLT. Transplantation was performed for a range of diseases including primary biliary cirrhosis (n Å 4), autoimmune hepatitis (n Å 4), primary Abbreviations: OLT, orthotopic liver transplantation; PCR, polymerase chain reacsclerosing cholangitis (n Å 2), cryptogenic cirrhosis (n Å 3), fulmition; SCT, stem cell transplantation; STR, short tandem repeats. nant hepatic failure (n Å 3), and alcohol-related cirrhosis (n Å 1).