Characteristic patterns of complement deposition in NMOSD, MOGAD, and MS

Area of Science:

• Neuroimmunology
• Pathology

Background:

• The complement system plays a role in CNS inflammatory demyelinating diseases (IDDs).
• Its specific involvement in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and multiple sclerosis (MS) remains unclear, unlike in neuromyelitis optica spectrum disorders (NMOSDs).

Purpose of the Study:

• To histopathologically assess complement system involvement in NMOSD, MOGAD, and MS.
• To differentiate the roles of complement deposition in the pathogenesis of these IDDs.

Main Methods:

• Immunohistochemistry was used to examine CNS tissues from patients with NMOSD, MOGAD, and MS.
• Deposition of complement components C4d, C3d, and C9neo was analyzed in relation to lesion characteristics.

Main Results:

• NMOSD showed a characteristic perivascular complement deposition pattern in astrocyte-lytic lesions.
• MOGAD exhibited variable C9neo deposition, distinguishing between types A (preserved oligodendrocytes) and B (oligodendrocyte loss).
• MS displayed C4d deposits on myelin sheaths in peri-plaque white matter, decreasing with lesion activity.

Conclusions:

• Distinct complement deposition patterns in NMOSD, MOGAD, and MS suggest different underlying pathogenetic mechanisms.
• Complement activation is a key feature with specific histopathological correlates in these CNS inflammatory demyelinating diseases.