The HLA 8.1 ancestral haplotype in schizophrenia: dual implication in neuro-synaptic pruning and autoimmunity?

Schizophrenia (SZ), a neurodevelopmental disorder, is one of the most severe and common psychiatric conditions, affecting globally 1% of adult population. Stemming from complex gene-environment interactions, in a significant subset of patients, SZ is characterized by immune dysfunctions that include early inefficient anti-infectious responses as well disease-associated chronic low-grade inflammation and comorbid autoimmune conditions (1). In such intersections between infection, inflammation and autoimmunity, the key genetic platform for both innate and adaptive immune processes is the major histocompatibility complex (MHC) which encompasses the prominent human leukocyte antigen (HLA) region. The HLA system is the most polymorphic region of the human genome and its allelic diversity is essential for antigen presentation to immune effector cells and downstream humoral and cellular immune responses. Hence, characterizing the HLA allelic diversity allows not only to evaluate the potential genetic relationship between the HLA system and a given disease but also to understand its impact on pathophysiological processes (2).