Background:
Schizophrenia is a complex and debilitating mental disorder
with strong heritability. Its pathogenesis involves immune dysregulation. Interleukin 15
and interleukin 15 receptor alpha(IL-15Rα) are classical immune molecules. They also
help maintain normal brain function, leading to our hypothesis that IL-15Rα gene(IL-
15RA) variants contribute to the pathogenesis of schizophrenia.
Objective:
We determine whether the genetic variants of IL-15RA are associated with
the development and progression of schizophrenia and whether IL-15RA single
nucleotide polymorphism(SNP) plays a key role in downstream signaling transduction.
Methods and results:
We sequenced IL-15RA exon from 132 Chinese schizophrenic
patients and identified a rare variant(rs528238821) in a patient diagnosed with catatonic
schizophrenia and ankylosing spondylitis(AS). We overexpressed this missense variant
in cells driven by pBI-CMV vector. The cells showed attenuated STAT3 phosphorylation
in response to interleukin15.
Conclusion:
IL-15RA mutation is rare in schizophrenic patients but interfered with IL-
15Rα intracellular signal transduction. Given the similarity of symptoms of catatonic
schizophrenia and the known phenotype of IL-15Rα knockout mice, gene variation might
offer diagnostic value for sub-types of schizophrenia.
Production of Bioactive Soluble Interleukin-15 in Complex with Interleukin-15 Receptor Alpha from a Conditionally-Replicating Oncolytic HSV-1
