Role of Centromeric and Telomeric Haplotypes of Killer-Cell Immunoglobulin-Like Receptors (KIRs) in Disease Susceptibility: A Research Review.

The immune regulatory functions of killer-cell immunoglobulin-like receptors (KIRs) become important through their ability to control natural killer (NK) cell function by interacting with human leukocyte antigen (HLA) molecules. Increasing scientific evidence indicates KIR haplotypes exist in two sets, namely, centromeric (Cen) and telomeric (Tel), which deliver unique effects to immune response function. Unlike traditional A/B KIR haplotype classification, this review emphasizes Cen and Tel subdivisions to provide a more nuanced understanding of gene linkage, functional diversity, and their relevance to autoimmune diseases, infections, transplantation outcomes, and pregnancy complications. It focuses on the coexpression of specific KIR genes driven by linkage disequilibrium, deliberately excluding studies limited to individual KIR alleles or classical haplotypes. Certain KIR configurations demonstrate significant influence on diseases through disease risk and also impact immune tolerance processes as well as resulting clinical outcomes. Our investigation through the literature revealed the relationship between Cen and Tel KIR haplotypes and rheumatoid arthritis, systemic lupus erythematosus (SLE), syphilis, and both hematopoietic stem cell transplantation (HSCT) and recurrent pregnancy loss (RPL). Researchers documented how Cen and Tel KIRs operate as either activating or inhibitory receptors in their study. However, few researches have studied the effect of Cen-Tel KIR haplotypes on the occurrence of diseases. There is a pressing need for research to focus on comprehensive KIR haplotyping analysis, as it holds the potential to enhance transplantation risk prediction, advance understanding in reproductive biology, uncover the pathogenesis of certain infectious diseases, and shed light on autoimmune-related disorders. Ultimately, the insights gained from Cen-Tel KIR haplotype analysis may serve as a foundation for developing targeted immunotherapeutics and personalized treatment strategies.