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Activation of the complement system is an important component of immune responses during inflammation. Complement activation is also involved in critical neurodevelopmental processes including synaptic elimination (Stevens et. al., Cell 2007). The presence of activation of neuroimmune pathways in brain tissues of patients with autism suggests complement activation may play pathogenic roles in autism.
Objectives: To determine whether complement activation is part of the immune mechanisms associated with neuropathological changes in autism
Methods: Immunopathological studies were performed in brain tissues from 11 patients previously diagnosed with autism and age-matched controls obtained from the Autism Tissue Project. Frontal, anterior cingulated and cerebellum tissue samples were used for immunostaining with specific antibodies that recognize proteins of the complement system including a membrane complex attack marker (C9neo). Co-localization studies with neuronal and neuroglial markers were also used to establish the localization and pattern of immunostaining.
Results: Immunoreactivity for the membrane complex attack (C9neo) was noted in 4 of 11 samples from cerebellum of patients with autism. Immunostaining with C9 neo was seen predominantly in neurons of the Purkinje cell layer and perineuronal compartment. Immunostaining appeared to be localized in Purkinje neurons and microglia processes within the perineuronal compartment. Other proteins associated with complement such as C1q was noted but the magnitude and patterns of staining was variable.
Conclusions: Activation of the complement system occurs in a subset of patients with autism and the pattern of distribution coincides with the involvement of cerebellum, an area of the brain affected in patients with autism as shown by neuropathological and neuroimaging studies. The presence of complement activation may be associated with pathogenic processes leading to neuronal degeneration and neuroinflammation.