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GRAFT VERSUS HOST DISEASE (GVHD) FOLLOWING LIVER TRANSPLANTATION: AN UNCOMMON APPLICATION OF CHIMERISM ANALSYSIS BASED ON STRs.
Tirza Klein PhD , Don Kristt MD , Ronit Narinski BS , Ruth Rahamimov MD , Alex Yussim MD and Eitan Mor MD . Petach Tikvah Israel, Rabin Medical Center, 49100, Tissue Typing Laboratory and Petach Tikvah Israel, Rabin Medical Center, 49100, Organ Transplantation .

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GVHD occurs as a result of the maturation of immuno-competent lymphocytes derived from the donor that initiate attack on a number of tissue targets in the recipient, which represents an unusual type of cellular chimerism. A recent case illustrates these laboratory strategies for diagnosis of cellular chimerism. A 51 y.o. women required transplantation because of Hepatitis C-related cirrhosis. Although transplanted without significant complications, after 4 weeks a diffuse maculo-papular skin rash appeared, which rapidly progressed to a state of “diffuse epidermal damage with eosinophilia”. The findings were consistent with drug eruption or GVHD, so that assessing the patient’s chimeric status, using molecular methods, was therefore required to establish the diagnosis of GVHD.
In the laboratory, chimerism among the patient’s peripheral blood cells was estimated by examining their DNA. Using PCR-SSP both donor and recipient HLA alleles were minimally detectable. However, DNA analysis of the bone marrow of the patient confirmed these results, and suggested that the extent of chimerism among marrow cells was greater than that detected in the peripheral blood. Computation of the % Donor Chimerism, based on STRs, showed four peaks both in marrow and peripheral blood, quantitatively confirmed the chimeric status. The analysis was facilitated by using our newly developed software application, Chimer-track.
This unusual case illustrates the crucial role for the quantitative determination of chimeric status in the definitive diagnosis of GVHD. Additionally, in the context of immunological tolerance, chimerism analysis may provide a basis to avoid therapeutic oversuppression.