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Saturday, May 17, 2008
Champagne Terrace/Bordeaux (Novotel London West)
Background: There is evidence of enhanced immune activity in post-mortem brain specimens from subjects with autism spectrum disorders (ASD) as well as immune dysregulation and autoimmune phenomena in the peripheral circulation. However, the exact nature and extent of the immune dysregulations in ASD have yet to be fully characterized. Natural killer (NK) cells, in particular, may play an important role in the development and course of neurodevelopmental disorders such as ASD.
Objectives: Previously, we performed a genomic screen in peripheral blood obtained from 35 children with confirmed ASD and 12 matched typically developing control children. Gene expression of NK cell receptors and NK-related effector molecules, such as granzyme B and perforin, were significantly upregulated in ASD compared with controls. Expanding on these initial studies, we carried out functional and cellular analysis of NK cells in ASD.
Methods: We performed NK cytotoxicity assays and flow cytometric analysis of NK effector molecules on blood obtained from 17 children with ASD and 16 matched typically developing general population controls enrolled in the CHARGE study.
Results: Flow cytometric analysis of NK effector molecules demonstrated that there was increased production of perforin, granzyme B, and interferon gamma (IFNγ) under resting conditions in children with ASD compared with controls (p<0.01). However, following stimulation in the presence of NK specific K562 target cells, the ability of NK cells from children with ASD to kill target cells was significantly reduced compared with controls (p<0.02). Furthermore, under similar stimulation conditions the presence of perforin, granzyme B, and IFNγ in NK cells from ASD children was significantly reduced compared with controls (p<0.001).
Conclusions: These findings suggest possible dysfunction of NK cells in children with ASD. Abnormalities in NK cells may represent a susceptibility factor in ASD and may predispose to the development of autoimmunity and/or adverse neuroimmune interactions during critical periods of development.
Objectives: Previously, we performed a genomic screen in peripheral blood obtained from 35 children with confirmed ASD and 12 matched typically developing control children. Gene expression of NK cell receptors and NK-related effector molecules, such as granzyme B and perforin, were significantly upregulated in ASD compared with controls. Expanding on these initial studies, we carried out functional and cellular analysis of NK cells in ASD.
Methods: We performed NK cytotoxicity assays and flow cytometric analysis of NK effector molecules on blood obtained from 17 children with ASD and 16 matched typically developing general population controls enrolled in the CHARGE study.
Results: Flow cytometric analysis of NK effector molecules demonstrated that there was increased production of perforin, granzyme B, and interferon gamma (IFNγ) under resting conditions in children with ASD compared with controls (p<0.01). However, following stimulation in the presence of NK specific K562 target cells, the ability of NK cells from children with ASD to kill target cells was significantly reduced compared with controls (p<0.02). Furthermore, under similar stimulation conditions the presence of perforin, granzyme B, and IFNγ in NK cells from ASD children was significantly reduced compared with controls (p<0.001).
Conclusions: These findings suggest possible dysfunction of NK cells in children with ASD. Abnormalities in NK cells may represent a susceptibility factor in ASD and may predispose to the development of autoimmunity and/or adverse neuroimmune interactions during critical periods of development.