Sensitization to OKT3 monoclonal antibody in heart transplantation: correlation with early allograft loss.
Because administration of murine monoclonal anti-CD3 antibody (OKT3) may result in the formation of human antimouse antibody, which complexes with OKT3, we conducted this study to assess the incidence and effect of human antimouse antibody formation during prophylactic administration of OKT3 in heart transplantation. Human antimouse antibody developed in eight of 55 (14%) cardiac allograft recipients receiving OKT3 prophylaxis as measured by enzyme-linked immunosorbent assay. Additionally, two recipients had an inexplicable rise in CD3+ lymphocytes during therapy without detectable antibody. The outcome of these 10 sensitized recipients was compared with that of 45 nonsensitized recipients. Age, preoperative diagnosis, hemodynamics, and the need for intravenous inotropes or mechanical assistance before transplantation were similar in both groups. No female patients were in the sensitized group, whereas 33% of the nonsensitized group were female patients. A trend toward greater sensitization when prophylaxis was extended to 21 days (28%) compared with the more conventional 14-day administration (10%) was not statistically significant. Retransplantation because of rejection was required in a single patient in each group. Allograft survival was significantly lower by 3 months in the sensitized group, and allograft loss caused by rejection selectively accounted for that difference. In survivors, rejection frequency and infectious complications were similar. These findings suggest that sensitization to OKT3 occurs at low frequency after prophylactic administration in heart transplantation but is associated with an increased frequency of graft loss because of rejection.
O'Connell
J B
JB
Utah Transplantation Affiliated Hospitals Cardiac Transplant Program, University of Utah Medical Center, Salt Lake City 84132.
Renlund
D G
DG
Hammond
E H
EH
Wittwer
C T
CT
Yowell
R L
RL
DeWitt
C W
CW
Jones
K W
KW
Gay
W A
WA
Menlove
R L
RL
Bristow
M R
MR
D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007165:Immunosuppression Therapy; D015994:Incidence; D008297:Male; D051379:Mice / Q000276:immunology; D008875:Middle Aged; D016853:Muromonab-CD3; D013997:Time Factors
D000906:Antibodies; D000911:Antibodies, Monoclonal; D016853:Muromonab-CD3