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REVIEW: Immunogenetic Factors of Neurodegenerative Diseases: The Role of HLA Class II

M. P. Aliseychik1,2,3,a*, T. V. Andreeva1,2, and E. I. Rogaev1,2,3,b,c*

1Vavilov Institute of General Genetics, Russian Academy of Sciences, Department of Genomics and Human Genetics, 119991 Moscow, Russia

2Center for Genetics and Genetic Technologies, Department of Biology, Lomonosov Moscow State University, 119192 Moscow, Russia

3Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01655, USA

* To whom correspondence should be addressed.

Received May 28, 2018; Revision received June 21, 2018
An increase in the life expectancy during the last decades in most world countries has resulted in the growing number of people suffering from neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and others. Familial forms of neurodegenerative diseases account for 5-10% of all cases and are caused by mutations in specific genes often resulting in pathological protein deposition. The risk factors for neurodegeneration include trauma, lifestyle, and allelic variants of disease-associated genes with incomplete penetrance. Many of these gene variants are located in immunity-related loci, particularly in the human leukocyte antigen locus (HLA class II) coding for proteins of the major histocompatibility complex class II (MHCII). HLA class II plays a key role in the antigen presentation and is expressed in microglial cells. Microglia is a component of innate immunity. On the one hand, microglial cells phagocytize pathological protein deposits; on the other hand, they produce proinflammatory factors accelerating neuronal death. The involvement of adaptive immunity mechanisms (antigen presentation, T cell response, antibody production) in the development of neurodegenerative diseases remains unclear and requires further research, including more detailed studies of the role of identified HLA class II genetic variants.
KEY WORDS: human leukocyte antigen, major histocompatibility complex class II, neurodegeneration, Alzheimer’s disease, Parkinson’s disease, genome-wide association study

DOI: 10.1134/S0006297918090122