Mycophenolic mofetil reduces the HLA antibody response of children to valved allograft implantation.
BACKGROUND
Valved allografts induce a brisk, broadly reactive human leukocyte antigen (HLA) antibody response in children after implantation. Mycophenolic mofetil (MMF) is a powerful immunosuppressant that inhibits the proliferation of both T cells and B cells and has been reported to possibly reduce HLA panel reactive antibody (PRA) in sensitized transplant recipients.


METHODS
The purpose of this study was to determine whether MMF can blunt the HLA antibody response to valved allografts in children. Eight patients completed (of 28 approached) a pilot study to determine the effects of 3 months of twice daily MMF (600 mg/m(2)/dose) on the HLA antibody response measured before surgery, at 1 month, and at 3 months after implantation. Patients were 7.5 +/- 4 yrs old (mean +/- standard deviation [SD]), with 5 patients undergoing repair of tetralogy of Fallot, 2 Ross procedures, and 1 aortic valve replacement.


RESULTS
In contrast to historical controls with a virtual 100% HLA class I PRA response to valved allograft implantation, MMF markedly decreased the HLA class I antibody response at 1 and 3 months postimplantation. In 6 cases where the HLA type of the donor was defined, PRA specificity correlated with incompatible antigens on the allograft. One patient withdrew after 2 weeks due to a sinus infection that was successfully treated with oral antibiotics, and 3 patients had a transient adverse effect of postoperative vomiting.


CONCLUSIONS
This study demonstrates the ability to pharmacologically abrogate the HLA class I antibody response to valved allograft implantation in children using MMF.
Shaddy
Robert E
RE
Department of Pediatrics, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, Utah 84113, USA. robert.shaddy@ihc.com
Fuller
Thomas C
TC
Anderson
Jeffrey B
JB
Lambert
Linda M
LM
Brinkman
Maureen K
MK
Profaizer
Tracie
T
Hawkins
John A
JA
D000917:Antibody Formation / Q000187:drug effects; D001323:Autoantibodies / Q000032:analysis*; D019917:Blood Vessel Prosthesis Implantation; D002648:Child; D002675:Child, Preschool; D006330:Heart Defects, Congenital / Q000601:surgery*; D019918:Heart Valve Prosthesis Implantation; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010865:Pilot Projects; D014184:Transplantation, Homologous
D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid