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Potential Autoepitope within the Extracellular Region of Contactin-Associated Protein-like 2 in Mice
Demian F Obregon1, Yuyan Zhu1, Antoinette R Bailey1
1Rashid 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.
Aims:
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.
Methodology:
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.
Conclusion:
Taken together, these data suggest that CNTNAP2 contains a potential autoepitope within the extracellular region.
Insights
Researchers found that contactin-associated protein-like 2 (CNTNAP2) has a potential autoepitope. Antibodies targeting this region were detected in children with autism, suggesting a link between CNTNAP2 autoimmunity and autism spectrum disorder.
Area of Science:
- Neuroimmunology
- Molecular Biology
- Genetics
Background:
- Contactin-associated protein-like 2 (CNTNAP2) is implicated in autoimmune encephalitis, neuromyotonia, and genetic autism.
- The role of CNTNAP2 in autoimmune disorders and autism requires further investigation.
Purpose of the Study:
- To identify potential autoepitopes within the CNTNAP2 protein.
- To investigate the presence of antibodies against CNTNAP2 in children with autism.
Main Methods:
- Identification of CNTNAP2 sequence-similar regions (CSSRs) from human pathogens.
- Analysis of sera from autistic and control children for anti-CSSR antibodies.
- Evaluation of a candidate CSSR in a mouse model of acute infection.
Main Results:
- Antibodies binding to discrete regions of CNTNAP2 were found in sera from both autistic and control children.
- In a mouse model, a CNTNAP2-derived CSSR induced anti-CNTNAP2 antibodies, inflammation, T-cell infiltration, and motor dysfunction.
Conclusions:
- CNTNAP2 contains a potential autoepitope within its extracellular region.
- These findings suggest a possible autoimmune component involving CNTNAP2 in autism spectrum disorder.
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