Heterogeneous alterations in human alloimmunity associated with immunization.
BACKGROUND
The presence of alloantibodies and/or alloreactive T cells in a patient prior to a transplant can impact graft outcome. Environmental factors, including therapeutic vaccinations, may influence the strength and/or specificity of alloimmunity.


METHODS
To address this issue, we prospectively evaluated the effects of two different immunization protocols in human subjects on cellular alloimmunity using an IFNgamma ELISPOT assay and on alloantibody reactivity by flow cytometric analysis of HLA-coated beads.


RESULTS
Vaccination/immunization was associated with augmentation of cellular and/or humoral alloimmune reactivity in >50% of the test subjects. The effects were heterogeneous in that some detected increases were transient, peaking 30-60 days postimmunization, whereas others persisted for the length of the study. Antibodies reactive to the immunizing agent did not cross react with the detected alloantibodies, suggesting that the augmentation of alloimmune reactivity was most likely due to a nonspecific adjuvant effect from the vaccine.


CONCLUSIONS
Therapeutic vaccinations can alter the strength of cellular and humoral alloimmunity in humans. The results suggest that serial immune monitoring of alloreactivity might be beneficial when immunizations are administered to potential transplant recipients.
Roddy
Meagan
M
Department of Immunology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Clemente
Michael
M
Poggio
Emilio D
ED
Bukowski
Ronald
R
Thakkar
Snehal
S
Waxenecker
Gunter
G
Loibner
Hans
H
Himmler
Gottfried
G
Hricik
Donald E
DE
Heeger
Peter S
PS
D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000276:immunology; D015551:Autoimmunity; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005770:Gastrointestinal Neoplasms / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000737:chemistry; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization / Q000009:adverse effects*; D007518:Isoantibodies / Q000096:biosynthesis*; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000379:methods*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014611:Vaccination
D016207:Cytokines; D006680:HLA Antigens; D007518:Isoantibodies