"Natural" human leukocyte antigen antibodies found in nonalloimmunized healthy males.

BACKGROUND: Human leukocyte antigen (HLA) antibodies were normally not found in subjects who have not been immunized by pregnancies, transfusions, or transplants. But with new methodology, we now see that HLA antibodies are often found in nonalloimmunized males. METHODS: The sera of 424 healthy male donors were tested with single antigen Luminex beads. RESULTS: Human leukocyte antigen antibodies were detected in 63% of 424 male blood donors when a fluorescent value of more than 1000 was used as the cutoff. Antibodies to class I was found in 42%, class II in 11% and both in 12%. Five males who were tested eight times over a 6-month period consistently had the same specificity at similar strength levels at each testing. The antibodies reacted with specificities that are rare in the general population: 18.9% had antibodies to A*3002; more than 10% had antibodies to A*3101, B76, B*8201, and Cw*1701. About half of the donors with antibodies had one or two specificities; the other half had three or more specificities. Among those with class II specificities, 20.5% had antibodies to DPA1*0201/DPB1*0101, and 10.8% to DQA1*0503/DQB1*0301. Because the above data were obtained by testing sera of 424 Mexican donors, as a check, 29 males in Los Angeles were tested and shown to have similar specificities at roughly similar frequencies. CONCLUSIONS: Normal males were found to have HLA antibodies to infrequent HLA specificities. It is likely that these HLA antibodies are produced to cross-reactive epitopes found in microorganisms, ingested proteins and allergens-making them natural antibodies.

Epitopes of HLA antibodies found in sera of normal healthy males and cord blood.

This chapter defines epitopes targeted by antibodies in the sera of two populations of healthy normal males and in cord blood samples from a third population. These epitopes are accessible for antibody binding on either the intact or dissociated forms of recombinant HLA class I single antigens. Sixty percent of these epitopes are defined by hidden amino acids, and are therefore designated as cryptic epitopes. All sera were tested in parallel, using single antigen beads that bore either intact or dissociated recombinant HLA antigens. Ninety-six HLA class I epitopes were characterized as epitopes of these antibodies. More than half were private epitopes, and the rest were shared by two-to-18 HLA antigens. Fifty-eight (60%) epitopes were accessible on dissociated HLA antigens. Of these, 41 were defined by hidden amino acids, 13 by at least one hidden amino acid in addition to exposed amino acids, and four were defined by exposed amino acids. Almost all epitopes were found exclusively on either A-, B-, or C-locus antigens--except for one inter-locus epitope. Antibodies with nearly identical specificities were found in all three of the tested populations. Most of these antibodies target epitopes that are accessible only on the dissociated forms of the HLA class I antigens. Specificities of such antibodies are unavoidably detected when testing for specificities of alloantibodies so it may be necessary to clearly differentiate the two forms of antibody. The relevance of these antibodies in transplantation is not yet known. But even if they are shown to be irrelevant to graft rejection, awareness of the newly identified epitopes could prove useful in avoiding unnecessary exclusion of potential transplant donors.