Rett syndrome: An autoimmune disease?

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting mostly females, characterized by intellectual deficit, loss of purposeful hand use, motor impairment, breathing disorders, and epilepsy.
• Mutations in the methyl-CpG binding protein 2 (MECP2) gene cause up to 95% of RTT cases. MECP2 plays a role in immune response, with MECP2 gene polymorphisms linked to autoimmune diseases.
• Previous research identified systemic redox imbalance, chronic inflammation, interstitial lung disease, and erythrocyte changes in RTT, alongside cytokine dysregulation.

Purpose of the Study:

• To review current evidence regarding the potential autoimmune component in Rett syndrome.
• To explore the relationship between MECP2 gene mutations, immune dysfunction, and autoimmune markers in RTT.

Main Methods:

• Review of existing scientific literature and studies on Rett syndrome, MECP2 gene, immune response, and autoimmune diseases.
• Analysis of findings related to cytokine dysregulation and autoantibodies in RTT patients.

Main Results:

• Elevated levels of anti-N-glucosylation (N-Glc) IgM serum autoantibodies, specifically anti-CSF114(N-Glc) IgMs, were detected in a significant number of RTT patients.
• Antineuronal antibodies have also been previously observed in RTT patients.
• Evidence suggests a link between MECP2 gene polymorphisms and various autoimmune conditions.

Conclusions:

• The presence of specific autoantibodies and the association of MECP2 with immune dysfunction suggest a potential autoimmune component in Rett syndrome.
• Further research is warranted to elucidate the precise role of autoimmunity in RTT pathogenesis and its implications for treatment.