Unexpected frequencies of HLA antibody specificities in the sera of pre-transplant kidney patients.
1. We utilize single-antigen beads to test 103 pre-transplant patients to discern HLA antibody specificity frequencies. 2. Overall, we found much higher levels of immunization to HLA than anticipated, particularly rare specificities. We postulate that the presence of epitopes and mismatching on epitopes are responsible for these higher levels of immunization. 3. Two models were generated: (A) The first was an antigen mismatch model representing the traditional theory that higher rates of immunization to an antigen would occur with a higher incidence of the antigen within the population. This model was based on published gene frequencies (4), which were converted into antigen frequencies. (B) The second model was an epitope mismatch model based on published gene frequencies (4) as well as experimentally proven epitopes (3). 4. These two models were then compared with observed antibody specificity frequencies. The antigen mismatch model consistently underestimated observed frequencies. On the other hand, the epitope mismatch model seems to be a much better representation of observed frequencies. 5. In conclusion, we bring attention to the occurrence of higher-than-expected frequencies of antibodies against HLA, especially rare antigens like A43 and B76, and we show that mismatched epitopes might provide a plausible explanation for these observed high frequencies.
Idica
Adam
A
One Lambda, Inc., Canoga Park, CA, USA.
Sasaki
Nori
N
Hardy
Steven
S
Terasaki
Paul
P
D000918:Antibody Specificity; D000939:Epitopes / Q000032:analysis / Q000097:blood; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D007519:Isoantigens / Q000097:blood; D016030:Kidney Transplantation / Q000276:immunology*; D011336:Probability
D000939:Epitopes; D006680:HLA Antigens; D007518:Isoantibodies; D007519:Isoantigens