Microvascular alterations and the role of complement in dermatomyositis

Area of Science:

• Immunology
• Neurology
• Pathology

Background:

• Dermatomyositis involves perifascicular muscle fiber atrophy, with proposed causes including ischemia, interferon activity, and vessel occlusion.
• The role and trigger of complement activation in dermatomyositis microvascular injury remain unclear.

Purpose of the Study:

• To investigate the association between perifascicular atrophy and microvascular changes in dermatomyositis.
• To identify the complement pathway involved in dermatomyositis pathogenesis and the trigger for its activation.

Main Methods:

• Assessed capillary and transverse vessel density in dermatomyositis patients and controls.
• Examined vascular deposits of IgG, IgM, and the complement C5b-9 membrane attack complex (MAC) in dermatomyositis specimens.
• Compared complement activation pathways in dermatomyositis, lupus nephritis, and Duchenne dystrophy.

Main Results:

• Perifascicular atrophy consistently correlated with reduced capillary and transverse vessel density.
• C5b-9 MAC deposits were found in 31/50 dermatomyositis specimens, primarily in endomysial microvessels.
• Complement activation in dermatomyositis, similar to Duchenne dystrophy, involved the classical pathway, indicated by C1q and C4d co-localization with C5b-9.

Conclusions:

• Focal microvascular depletion is a consistent feature of perifascicular atrophy in dermatomyositis.
• Microvascular MAC deposits in dermatomyositis stem from classical complement pathway activation.
• The classical pathway is triggered by C1q directly binding to injured endothelial cells.