The HLA-B*57:01 Haplotype, Genetic Key Linking Innate Immunity and Longevity

In our recent research on AIDS Elite controllers, we demonstrated that the HLA-B*57:01 allele is part of an extensive MHC haplotype associated with impaired MICA/MICB function. Considering the pivotal role of natural killer (NK) cells and innate immunity in fighting cancer and infectious diseases, we investigated whether this allele could also influence human longevity. To this end, we performed a multinational European study including 2,597 centenarians and 9,973 controls. We found that HLA-B*57:01 was consistently less frequent in the European centenarian cohorts compared with the corresponding controls (OR ≈ 0.68, p < 0.0005). These findings provide the first in vivo genetic evidence that innate immunity and NK cell function are key components of human longevity.