Utility of posttransplantation panel-reactive antibody measurements for the prediction of rejection frequency and survival of heart transplant recipients.
METHODS
Seventy-six heart transplants in 73 patients were studied for the formation of lymphocytotoxic panel-reactive antibodies after transplantation. Treatment of patient serum with dithioerythritol was used to discriminate between antibodies of the immunoglobulin M and immunoglobulin G isotypes. Human leukocyte antigen specificities of immunoglobulin G panel reactive antibodies were determined by the pattern of reactivity with the cell panel used in the panel-reactive antibodies determinations. A total of 465 panel-reactive antibodies determinations were made during the first year after transplantation.


RESULTS
Mean panel-reactive antibodies values were highest during the first posttransplantation month. Positive dithioerythritol-treated panel-reactive antibodies values were rare after the first month after transplantation. Multivariable analysis indicated that previous pregnancy and positive cytomegalovirus serologic analysis predicted a higher dithioerythritol-treated panel-reactive antibodies within the first 3 months. No decrease in actuarial survival, increase in cumulative rejection episodes, or increase in the incidence of coronary artery disease at 1 year was seen in patients with a standard panel-reactive antibodies greater than 10% or among patients with dithioerythritol-treated panel-reactive antibodies greater than 0%. A significant and major increase in rejection-related death or retransplantation occurred among 11 patients in whom donor human leukocyte antigen specific antibodies of the immunoglobulin G isotype were detected during the first posttransplantation year (p = 0.02). Two of the 11 patients died of refractory rejection and 3 and 6 months after transplantation, whereas one patient underwent retransplantation for refractory rejection at 13 months and subsequently died.


CONCLUSIONS
(1) Posttransplantation serial standard panel-reactive antibodies or dithioerythritol-treated panel-reactive antibodies are not predictive of rejection-related mortality unless the specificity is determined to be antidonor HLA; (2) routine dithioerythritol-treated panel-reactive antibodies studies are advisable during the first month after transplantation, and, if positive (> 10%), antidonor human leukocyte antigen specificity should be determined; (3) detection of recipient immunoglobulin G anti-donor human leukocyte antigen antibodies after heart transplantation identifies a group at high risk for serious allograft rejection and should prompt more intensive rejection surveillance and consideration for additional immunotherapy.
George
J F
JF
Department of Surgery, University of Alabama at Birmingham 35294-0007, USA.
Kirklin
J K
JK
Shroyer
T W
TW
Naftel
D C
DC
Bourge
R C
RC
McGiffin
D C
DC
White-Williams
C
C
Noreuil
T
T
D000206:Actuarial Analysis; D000293:Adolescent; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004226:Dithioerythritol / Q000494:pharmacology; D000939:Epitopes; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007223:Infant; D007518:Isoantibodies / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012086:Reoperation; D012307:Risk Factors; D013997:Time Factors
D000961:Antilymphocyte Serum; D000939:Epitopes; D006680:HLA Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies; D004226:Dithioerythritol