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.