The enteric nervous system is a potential autoimmune target in multiple sclerosis.

Area of Science:

• Neuroimmunology
• Gastroenterology
• Autoimmune Diseases

Background:

• Multiple sclerosis (MS) is a chronic CNS autoimmune disease impacting young adults.
• Gastrointestinal dysfunction is common in MS but its link to the disease's autoimmune nature is unclear.
• The enteric nervous system (ENS) controls gut function.

Purpose of the Study:

• To investigate the role of the ENS in a mouse model of MS.
• To determine if ENS pathology is linked to autoimmune processes in MS.
• To explore potential diagnostic and therapeutic targets for MS-related gut dysfunction.

Main Methods:

• Immunohistochemistry and electron microscopy in a mouse model of MS.
• Immunoprecipitation and mass spectrometry to identify autoantigens.
• ELISA and analysis of human colon resectates from MS patients.

Main Results:

• ENS degeneration, gliosis, and neuronal loss occurred before CNS lesions and neurological symptoms in mice.
• Antibody-mediated pathology significantly reduced gastrointestinal motility.
• Autoantibodies against enteric antigens were found in MS patients, correlating with ENS degeneration in human colon samples.

Conclusions:

• Establishes a direct link between autoimmune attack on the CNS and ENS pathology in MS.
• Suggests ENS degeneration is an early event in MS immunopathogenesis.
• Highlights potential for new diagnostic and therapeutic strategies targeting the ENS in MS.