PMID- 14966423 OWN - NLM STAT- MEDLINE DCOM- 20040329 LR - 20041117 IS - 0041-1337 (Print) IS - 0041-1337 (Linking) VI - 77 IP - 3 DP - 2004 Feb 15 TI - Monitoring systemic donor lymphocyte macrochimerism to aid the diagnosis of graft-versus-host disease after liver transplantation. PG - 441-6 AB - BACKGROUND: The diagnosis of graft-versus-host disease (GvHD) after liver transplantation can be difficult because early symptoms are often nonspecific. In this study, the presence of donor lymphocyte macrochimerism in recipient peripheral blood was examined as a diagnostic aid for GvHD after cadaveric donor liver transplantation. METHODS: Between 1996 and 2002, 33 liver transplant recipients with a clinical suspicion of GvHD (skin rash, diarrhea, pyrexia, pancytopenia, or anemia, without an obvious alternative cause) were investigated for peripheral blood donor lymphocyte macrochimerism. Donor macrochimerism was determined at the time of first clinical presentation by a low-sensitivity polymerase chain reaction (PCR) to detect donor human leukocyte antigen (HLA) alleles using genomic DNA extracted from recipient peripheral blood. Where donor HLA alleles were detected, the percentage of donor T cells was quantified by two-color flow cytometric analysis using antibodies specific for mismatched donor and recipient HLA alleles. The relationship between the presence or absence of donor lymphocyte macrochimerism and final diagnoses based on clinical and histological criteria was examined. RESULTS: Seven of the 33 patients were PCR positive for donor HLA alleles. All had macrochimerism, with donor T lymphocyte levels ranging from 4% to 50% of circulating lymphocytes. All seven patients had normal liver function tests, skin rash, and diagnosis of GvHD histologically confirmed by skin or gut biopsies. Twenty-six patients were PCR negative, and, in 23, an alternative diagnosis was eventually established. The remaining three patients made a rapid and spontaneous recovery with no further symptoms suggestive of GvHD. CONCLUSIONS: Donor lymphocyte macrochimerism was present in all patients in whom the diagnosis of GvHD was confirmed. In patients with symptoms consistent with GvHD and a negative PCR for donor HLA, an alternative diagnosis was eventually established or the patients recovered spontaneously. Detection of donor HLA alleles in recipient peripheral blood by PCR is a useful diagnostic tool for GvHD after liver transplantation. FAU - Taylor, Anna L AU - Taylor AL AD - Department of Surgery, Addenbrooke's Hospital, Cambridge University Teaching Hospitals Trust, Cambridge, UK. FAU - Gibbs, Paul AU - Gibbs P FAU - Sudhindran, Surendran AU - Sudhindran S FAU - Key, Tim AU - Key T FAU - Goodman, Reyna S AU - Goodman RS FAU - Morgan, C Helen AU - Morgan CH FAU - Watson, Christopher J E AU - Watson CJ FAU - Delriviere, Luc AU - Delriviere L FAU - Alexander, Graeme J AU - Alexander GJ FAU - Jamieson, Neville V AU - Jamieson NV FAU - Bradley, J Andrew AU - Bradley JA FAU - Taylor, Craig J AU - Taylor CJ LA - eng PT - Journal Article PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (HLA Antigens) SB - IM MH - Aged MH - Alleles MH - Blood MH - Female MH - Graft vs Host Disease/*diagnosis MH - HLA Antigens/genetics MH - Humans MH - *Liver Transplantation MH - *Lymphocytes MH - Male MH - Middle Aged MH - Polymerase Chain Reaction MH - *Population Surveillance/methods MH - *Tissue Donors MH - *Transplantation Chimera EDAT- 2004/02/18 05:00 MHDA- 2004/03/30 05:00 CRDT- 2004/02/18 05:00 PHST- 2004/02/18 05:00 [pubmed] PHST- 2004/03/30 05:00 [medline] PHST- 2004/02/18 05:00 [entrez] AID - 00007890-200402150-00024 [pii] AID - 10.1097/01.TP.0000103721.29729.FE [doi] PST - ppublish SO - Transplantation. 2004 Feb 15;77(3):441-6. doi: 10.1097/01.TP.0000103721.29729.FE.