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

Myriam Rahmouni1, Cristina Giuliani2, Daniela Colucci2

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|October 24, 2025
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Summary
This summary is machine-generated.

The HLA-B*57:01 allele, linked to impaired immune function, was less common in European centenarians. This suggests natural killer (NK) cell function and innate immunity are crucial for human longevity.

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Area of Science:

  • Immunogenetics
  • Human Longevity
  • Innate Immunity

Background:

  • The HLA-B*57:01 allele is associated with impaired MICA/MICB function in AIDS Elite controllers.
  • Natural killer (NK) cells and innate immunity play critical roles in combating cancer and infectious diseases.

Purpose of the Study:

  • To investigate the potential influence of the HLA-B*57:01 allele on human longevity.
  • To determine if genetic factors related to innate immunity impact lifespan.

Main Methods:

  • A multinational European study was conducted.
  • The study included 2,597 centenarians and 9,973 controls.
  • Genotyping for the HLA-B*57:01 allele was performed.

Main Results:

  • The HLA-B*57:01 allele was significantly less frequent in European centenarians compared to controls (OR ≈ 0.68, p < 0.0005).
  • This finding was consistent across multiple European cohorts.

Conclusions:

  • The study provides the first in vivo genetic evidence linking innate immunity and NK cell function to human longevity.
  • The HLA-B*57:01 allele's reduced frequency in centenarians highlights the importance of robust innate immune function for exceptional lifespan.