Allele-Level KIR Polymorphism and Two-Locus Haplotypes in Elderly and Young Individuals From Southeastern Europe: Data From the 18th International HLA and Immunogenetics Workshop (IHIWS)

Abstract

Killer immunoglobulin-like receptors (KIRs) are central regulators of natural killer (NK) and T-cell function through interactions with HLA Class I ligands. Although KIR genes are highly polymorphic, their allele-level diversity and their potential role in healthy ageing remain incompletely characterized. In this study, we performed high-resolution, allele-level genotyping of 10 KIR genes in three ethnically distinct populations from Bulgaria, Romania, and Turkey. Each population was analysed separately, using unrelated healthy young individuals (≤ 35 years) and ethnically matched healthy elderly individuals (> 65 years); allele frequencies and two-locus KIR haplotypes were then compared between age groups. Across all populations, most KIR alleles showed similar distributions between young and elderly cohorts, consistent with a shared European allelic framework. In the Bulgarian cohort, only KIR3DL2*01001 showed a trend towards increased frequency among the elderly. In the Romanian cohort, healthy elderly individuals exhibited significant enrichment for KIR2DL2*00101 and KIR2DL3*00201, along with increased retention of the inhibitory receptors KIR2DL1, KIR2DL2, and KIR2DL3. In the Turkish cohort, several low-frequency alleles of the framework genes KIR3DL2 and KIR3DL3 showed age-associated trends but did not remain significant after multiple-testing correction. Haplotype analysis revealed that the Bulgarian allele-level association was largely captured within the KIR3DL1*00501~KIR3DL2*01001 haplotype, while multiple Romanian haplotypes carrying KIR2DL2*00101 were enriched in the elderly group. Independent analyses involving Poles also showed a largely shared allelic repertoire characteristic of all four European populations. These findings provide an exploratory assessment of KIR allele-level variation in healthy ageing and suggest that the preservation of specific inhibitory KIR configurations may represent an immunogenetic feature of healthy ageing in Southeastern European populations. However, these associations should be considered preliminary and require validation in larger cohorts before definitive conclusions can be made.