IMMUNOGENOMICS IN PRECISION MEDICINE: LINKING GENETIC VARIABILITY TO DISEASE SUSCEPTIBILITY AND THERAPEUTIC RESPONSE

Abstract

Immunogenomics has become an important part of precision medicine, as it helps to understand the effect of genetic variation on immune function, disease susceptibility and therapeutic response. This review covers the genetic structure of immune system genes, especially human leukocyte antigen, killer-cell immunoglobulin-like receptor, cytokine, complement and T-cell and B-cell receptor genes. It outlines the role of polymorphisms, structural variation, epigenetics and population-level evolutionary pressures in immune recognition and clinical outcomes. The review further examines the relationship between immune associated genetic polymorphisms and autoimmune diseases, infectious diseases, cancer as well as allergic or atopic diseases. The clinical relevance of immunogenomics in the fields of pharmacogenomics, immune checkpoint inhibitor response, vaccine responsiveness, and transplant compatibility are highlighted. Examples of established applications include HLA guided prevention of severe drug hypersensitivity, prediction of response to immunotherapy and enhanced donor–recipient matching. Next generation sequencing, high resolution HLA typing, single-cell immunogenomics, immune-receptor sequencing, multi-omics techniques, and AI and machine learning are also factored. Although significant advances have been made, the translation of clinical research is limited by polygenic complexity, lack of uniformity in analyses, population heterogeneity, cost, privacy issues and unequal access to genomic technologies. Further progress will demand for more heterogeneous cohorts, defined procedures, functional assays, transparent algorithms and robust integration of genomic, immunological and clinical data. Immunogenomics, thus, has a lot of potential in better predicting risk of disease, choosing treatment, monitoring treatment, and in the personalization of healthcare.