Six-year monitoring of the donor-specific immune response to cryopreserved aortic allograft valves: implications with valve dysfunction.
BACKGROUND
The immune rejection has been anticipated as one of the major causes of allograft aortic valve (AAV) degeneration. The purpose of this study was to prospectively serially measure the magnitude and evolution of the recipient anti-HLA class I antibody response up to 6 years from AAV implant and to correlate serologic data with valve performance by means of a concurrent echocardiographic survey.


METHODS
Cryopreserved AAVs were obtained from multiorgan HLA-typed donors. Nineteen patients younger than 50 years (mean age, 43.3 +/- 8 years) were prospectively studied. After successful surgery, all AAV recipient underwent at 3 and 6 months and each year postoperatively (mean follow-up, 71.9 months) concomitant serum sample collection and two-dimensional transthoracic echocardiography. The presence of anti-HLA antibodies was tested against a panel of lymphocytes obtained from 30 blood donors.


RESULTS
Progressive structural valve deterioration was seen in 6 patients (31.5%) of whom 4 (21%) were reoperated. All pretransplant recipients sera were panel-reactive antibody negative. Seventeen patients (89.4%) demonstrated significant panel-reactive antibody levels, which peaked at 6 months postoperatively, declined from 6 to 24 months, and slowly decreased afterward. In 14 of 19 cases (73.6%) donor-specific HLA antibodies were identified. A strong immunization (6-year persistence of panel-reactive antibody > 70% and peak panel-reactive antibody > 80%) was detected in 31.5% and 36.8% of recipients, respectively. Strong immunization was found to be significantly associated with progressive structural deterioration.


CONCLUSIONS
The immune reaction after cryopreserved AAV implantation is a peculiar long-lasting response occurring in the majority of recipients younger than 50 years of age. An association between a sustained and pronounced immunization and an aggressive AAV degeneration was observed.
Department of Cardiovascular Surgery, Centro Cardiologico Monzino IRCCS, Milan, Italy.
Giulio
G
Pompilio
GianLuca
G
Polvani
Giuseppe
G
Piccolo
Anna
A
Guarino
Angela
A
Nocco
Annalisa
A
Innocente
Massimo
M
Porqueddu
Luca
L
Dainese
Fabrizio
F
Veglia
Andrea
A
Sala
Paolo
P
Biglioli
D000293:Adolescent; D000328:Adult; D001021:Aortic Valve / Q000276:immunology / Q000637:transplantation*; D001705:Bioprosthesis; D015925:Cryopreservation; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006350:Heart Valve Prosthesis; D006801:Humans; D007114:Immunization; D007518:Isoantibodies / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009926:Organ Preservation / Q000379:methods; D011446:Prospective Studies; D014019:Tissue Donors; D020858:Tissue and Organ Harvesting / Q000379:methods; D014184:Transplantation, Homologous / Q000276:immunology*
D006680:HLA Antigens; D007518:Isoantibodies