Imcomp

A Comparison of Immunosuppression Levels Between Kidney and Liver Transplant Recipients using the Immunocompetence Assay

Introduction: Although there are similarities between the transplantation of livers and kidneys, many differences do exist. One striking example is found in the graft survival rates of the organs two or more years post-transplant. Both patient types show a sharp decline in graft survival rates after the first six months, but differ thereafter. Kidney grafts show a steady decline in survival rates whereas liver grafts are remarkably stable. The project thus attempts to solve the main question of why the survival rates of liver grafts are more stable over time than those of kidney grafts by focusing on possible differences in blood drug levels and immunocompetence as determined by the immunocompetence assay.

Methods: Blood from 78 kidney and 86 liver tx. recipients was drawn and analyzed for cyclosporine A (CYA) and FK506 levels.
Immunocompetence Assay Leukocytes from hemapharesis donor packs were separated into two "stimulator" samples: 1) depleted (D) of antigen presenting cells (APCs) and 2) undepleted (ND), which contained APCs in addition to T-cells. Patient leukocytes, "responders," were prepared by ficoll-hypaque separation and contained APCs.

The "responders" were cultured for six days with ND and D stimulator cell pairs from at least two donors as well as with PHA as a positive control and tissue culture medium (TCM) as a baseline for "at rest" cell proliferation. Cell proliferation was determined by measuring the incorporation of tritiated thymidine. Counts from stimulated responders that were at least three times the TCM baseline were considered positive, "+." Values between 2X and 3X TCM were assigned a "+." Counts below 2X were given a "-." Each responder received a score from ND/D stimulation resulting in a range of possible values:

			+/+,	+/+,	+/-,	+/-,	-/-
			--- increasing immunosuppression --->

For statistical purposes, the range was assigned numerical values from 4 (+/+) down to 0 (-/-).

Results:

				KIDNEY	LIVER	P Value (paired t-test: kidney vs. liver)
CYA level AVG (ng/ml)		232.82	263.39	0.205
FK506 level AVG (ng/ml)		9.77	8.08	0.285
IMCOMP value AVG		2.46	2.15	0.102

Discussion: Kidney vs. liver t-tests of CYA and FK506 levels showed no significant differences (P>0.05) although the liver patients were shown to be more immunosuppressed as evidenced by the IMCOMP averages. In addition, livers showed a greater level of suppression in twelve of the sixteen stimulators used (data not shown). Since all of the patients were being closely monitored for signs of rejection or organ failure, drug doses were continually changed to maintain optimal levels of immunosuppression. Under these conditions, liver tx. patients displayed a weaker response to alloantigen than did kidney tx. patients. This result merits further investigation of possible differential T helper subset activation. Analyzing cytokine secretion profiles may shed some light on whether or not Th2 cells are more prominent in the immune response of liver tx. patients than Th1 cells.

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