Genetic Factors in Neuroimmune Diseases

Neuroimmune diseases consist of a heterogeneous group of neurological disorders characterized by aberrant immune responses against either the central or the peripheral nervous system. Unlike monogenic diseases, neuroimmune disorders do not follow Mendelian patterns of inheritance, and their genetic basis has been elusive for decades. It has been only recently that novel methodologies of analysis, such as the genome-wide association study (GWAS) paradigm, have provided the tools for deciphering the complex genetic architecture proper of these disorders. Indeed, immunogenetic and epidemiological data suggest a polygenic model of inheritance in which the interplay between multiple genetic and environmental factors is crucial for disease risk. Among the different genetic determinants, the major histocompatibility complex (MHC) locus accounts for the highest component of genetic risk for the vast majority of neuroimmune disorders, suggesting that dysfunctions in the antigen presentation process likely play a pivotal role in their pathophysiology. However, further studies will be necessary to fully describe the multifactorial nature of such complex diseases and discover the full roster of molecular pathways associated with the different risk variants.