Potential Autoepitope within the Extracellular Region of Contactin-Associated Protein-like 2 in Mice.
OBJECTIVE
Implicated in autoimmune encephalitis, neuromyotonia and genetic forms of autism, here we report that contactin-associated protein-like 2 (CNTNAP2) contains a potential autoepitope within the extracellular region.


METHODS
CNTNAP2 sequence-similar regions (CSSRs) from human pathogens were identified. Sera from autistic and control children were obtained and analyzed for the presence of antibodies able to bind CSSRs. One such candidate CSSR was evaluated for evidence of autoimmune responses to CNTNAP2 in a mouse model of acute infection.


RESULTS
Autistic and control children sera contained antibodies able to discrete regions of CNTNAP2. In a murine model of acute infection, a CSSR derived from the N-terminal extracellular region of CNTNAP2 resulted in anti-CNTNAP2 antibody production, proinflammatory cytokine elevation, cerebellar and cortical white matter T-cell infiltration as well as motor dysfunction.


CONCLUSIONS
Taken together, these data suggest that CNTNAP2 contains a potential autoepitope within the extracellular region.
Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, MDT 14, 3515 East Fletcher Avenue, Tampa, Florida, 33613, USA.
Demian F
DF
Obregon
Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, MDT 14, 3515 East Fletcher Avenue, Tampa, Florida, 33613, USA.
Yuyan
Y
Zhu
Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, MDT 14, 3515 East Fletcher Avenue, Tampa, Florida, 33613, USA.
Antoinette R
AR
Bailey
Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, MDT 14, 3515 East Fletcher Avenue, Tampa, Florida, 33613, USA.
Samantha M
SM
Portis
Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, MDT 14, 3515 East Fletcher Avenue, Tampa, Florida, 33613, USA.
Huayan
H
Hou
Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, MDT 14, 3515 East Fletcher Avenue, Tampa, Florida, 33613, USA.
Jin
J
Zeng
Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, MDT 14, 3515 East Fletcher Avenue, Tampa, Florida, 33613, USA.
Saundra L
SL
Stock
Psychiatry and Behavioral Neurosciences, Rothman Center for Neuropsychiatry, Morsani College of Medicine, University of South Florida, 800 6 Street South, Box 7523, Saint Petersburg, Florida, 33701, USA ; Department of Pediatrics, Rothman Center for Neuropsychiatry, Morsani College of Medicine, University of South Florida, 800 6 Street South, Box 7523, Saint Petersburg, Florida, 33701, USA.
Tanya K
TK
Murphy
Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, MDT 14, 3515 East Fletcher Avenue, Tampa, Florida, 33613, USA.
Michael A
MA
Bengtson
Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, MDT 14, 3515 East Fletcher Avenue, Tampa, Florida, 33613, USA.
Jun
J
Tan
CNTNAP2; Caspr 2; autism; autoantibody; autoepitope; autoimmune; encephalopathy; molecular mimicry