Effect of mycophenolate mofetil therapy on lymphocyte activation in heart transplant recipients.
BACKGROUND
Mycophenolic acid is reported to provide effective immunosuppression by inhibiting inosine monophosphate dehydrogenase. In an attempt to monitor the effects of therapy with mycophenolate mofetil, we measured the expression of the activation markers CD25, CD38, CD69 and HLA-DR on lymphocytes of patients after heart transplantation.


METHODS
Thirty-six patients enrolled in the study were randomly assigned to one of two groups. Patients in the control group (n = 15) received cyclosporine, azathioprine and prednisone. Patients in the study group (n = 21) were switched from azathioprine to mycophenolate mofetil (MMF) 3 months after heart transplantation. The expressions of the activation markers CD25, CD38, CD69 and HLA-DR on B cells, T cells and natural killer (NK) cells in peripheral blood were determined by flow cytometry.


RESULTS
In patients treated with MMF a significant reduction of the B-cell count was observed in comparison to a healthy control group and patients under therapy with azathioprine. The decline of B cells in the MMF group started 3 months after onset of therapy and, after 1 year, was nearly halved. In addition, the percentages of CD38-positive B cells, activated T cells (CD4(+)/CD25(+), CD8(+)/CD38(+)) and HLA-DR-expressing NK cells were reduced during therapy with MMF.


CONCLUSIONS
Our studies have shown administration of MMF to be associated with a reduction of B lymphocytes and a downregulation of activation markers on B cells. In contrast to in vitro findings, our data indicate that the immunosuppressive effect of MMF in vivo is exhibited mainly on B cells.
Weigel
Guenter
G
Department of Cardiothoracic Surgery, University of Vienna Medical School, Vienna, Austria.
Griesmacher
Andrea
A
Karimi
Ali
A
Zuckermann
Andreas O
AO
Grimm
Michael
M
Mueller
Mathias M
MM
D036541:ADP-ribosyl Cyclase / Q000032:analysis; D051997:ADP-ribosyl Cyclase 1; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*; D011184:Postoperative Period; D015375:Receptors, Interleukin-2 / Q000032:analysis; D000099192:CD69 Antigens
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D006684:HLA-DR Antigens; D007168:IMP Dehydrogenase; D007166:Immunosuppressive Agents; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D009173:Mycophenolic Acid; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens; C498154:CD38 protein, human