CD26/dipeptidyl peptidase IV: a comparative study of healthy persons and kidney transplant recipients before and early after transplantation.

OBJECTIVES: Human CD26 is co-stimulatory for lymphocytes, circulates in a soluble form in blood (sCD26), and has intrinsic dipeptidyl peptidase IV (DPPIV) activity. Associations between CD26 expression on the surface of T cells (CD26+/CD3+) and acute rejection and between (CD26+/CD3+)/DPPIV and clinical immunosuppression have been reported. These results encouraged the investigation of CD26 as a potential biomarker to optimize immunosuppressive therapy. To better understand the significance of CD26, a comparative study of CD26 expression on CD3+ cells, sCD26 concentration, and DPPIV activity in healthy persons (HP) and kidney transplant recipients (KTR) was performed. DESIGN AND METHODS: Thirty-one HP and 34 KTR were included in the study. CD26+/CD3+ was determined by FACS, sCD26 concentration was determined by ELISA, and DPP activity was determined by spectrophotometry. For KTR, these parameters were studied on the day before transplantation (preTx) and 7±1days after transplantation (postTx). RESULTS: There was no significant difference in the CD26+/CD3+, sCD26, and DPPIV data regarding gender, donor type (16 living donors), delayed graft function (n=8), or presence of ≥4HLA mismatches (n=16). Compared to the HP data, preTx CD26+/CD3+ was 4.5-fold higher, sCD26 was 1.2-fold higher, and DPPIV showed no significant difference. PostTx, CD26+/CD3+ was 3.8-fold higher, and sCD26 and DPPIV decreased significantly, reaching lower values than that observed in HP. Re-transplanted patients (n=5) showed significantly lower preTx CD26+/CD3+ expression than patients receiving their first transplant. Patients with preemptive transplantation (n=7) showed higher postTx CD26+/CD3+ expression than patients on dialysis. CONCLUSIONS: CD26 expression on CD3+ cells was strongly increased in patients with end stage kidney disease compared to HP and remained high early postTx. The differences in sCD26 and DPPIV behavior compared to that of CD26+/CD3+ postTx may reflect a regulatory response to the new immunological situation and the effects of therapy.

Association between pharmacodynamic biomarkers and clinical events in the early phase after kidney transplantation: a single-center pilot study.

INTRODUCTION: Strategies based on monitoring pharmacodynamic effects are increasingly evaluated to individualize immunosuppressive therapy. In the present investigation, both drug-specific and general pharmacodynamic biomarkers were assessed and their association with clinical events early after kidney transplantation was examined. METHODS: Thirty-five de novo kidney transplant patients receiving basiliximab, enteric-coated mycophenolate sodium (2×720 mg/day), steroids, and tacrolimus (target: 6-8 µg/L) were included. Blood was drawn on days 7(±1) and 21(±2) after transplantation. Mononuclear leucocytes were isolated and the following parameters were investigated: inosine monophosphate dehydrogenase activity (high-performance liquid chromatography-diode array detection), cell proliferation (bromodeoxyuridine test), and CD marker cell surface expression (CD25, CD71, CD26) on stimulated (phytohemagglutinin 2.5 µg/10(6) cells) and nonstimulated CD3 cells. Acute rejection, gastrointestinal adverse effects, leucopenia, and infections were monitored over 3 months. RESULTS: There was no association between clinical events and inosine monophosphate dehydrogenase activity apart from patients with diarrhea showing a significantly higher inosine monophosphate dehydrogenase activity 2 hours after the enteric-coated mycophenolate sodium dose (P<0.05). Cell proliferation was significantly reduced in patients with leucopenia (P<0.05). CD71 expression was less inducible in patients with infections (P<0.05). A lower CD26 expression on non stimulated CD3 cells predicted freedom from rejection (Day 7; negative predictive value 100%). No associations were found between CD25 expression and events. CONCLUSIONS: A potential benefit of pharmacodynamic monitoring to optimize immunosuppressive combination therapy has been demonstrated. In particular, CD26 and CD71 may be promising biomarkers to assess adequate immunosuppression in the early phase after kidney transplantation. The results of this pilot study require verification in further trials with more patients and events as well as with different graft types.