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Membrane attack complex of complement in Henoch-Schönlein purpura skin and nephritis
S Kawana1, G H Shen, Y Kobayashi
1Department of Dermatology, Kitasato University School of Medicine, Kanagawa, Japan.
Insights
Complement activation and membrane attack complex (MAC) assembly occur in Henoch-Schönlein purpura (HSP) skin and kidney lesions. This suggests MAC plays a role in the vascular injury characteristic of HSP.
Area of Science:
- Immunology
- Pathology
- Nephrology
Background:
- Henoch-Schönlein purpura (HSP) is a systemic vasculitis.
- The role of complement activation in HSP pathogenesis is not fully understood.
Purpose of the Study:
- To investigate complement activation and membrane attack complex (MAC) assembly in HSP skin and nephritis lesions.
- To determine if MAC contributes to vascular injury in HSP.
Main Methods:
- Direct immunofluorescence using monoclonal antibodies.
- Detection of C5b-9 complex-related antigens, C5, C6, C7, C8, C9, and S protein.
Main Results:
- C5b-9 deposition, indicating MAC assembly, was found in the vascular walls of 11/15 HSP skin lesions.
- MAC components were detected in glomeruli of 2/4 HSP nephritis specimens, with S protein co-localization in the other two.
- The majority of C5b-9 in skin lesions represented the cytolytically active MAC.
Conclusions:
- Complement activation leading to MAC generation is likely involved in the pathogenesis of vascular injury in HSP skin lesions.
- MAC may also play a role in the pathogenesis of HSP nephritis.
- These findings highlight the significance of the complement system in HSP.
Abstract:
The present study using direct immunofluorescence with monoclonal antibodies to C5b-9 complex-related antigens was undertaken to determine whether complement activation in Henoch-Schönlein purpura (HSP) causes assembly of the membrane attack complex of complement (MAC) in skin and nephritis lesions. The deposition of C5, C6, C7, C8, C9, and C5b-9 neoantigens was noted in the vascular walls of papillary dermis and/or subpapillary dermal plexus of the vessels in 11 out of 15 patients with HSP. Their presence in vessel walls indicates complement activation which leads to terminal complement activation. There were small deposits of S protein at the same sites in three of the 11 skin specimens. Thus, the majority of C5b-9 demonstrated in HSP skin was the cytolytically active C5b-9 complex, MAC. Granular deposits of C5b-9 related antigens without S protein were also found in the capillary walls and mesangium of the glomeruli of two out of four specimens from patients with HSP nephritis; in the other two S protein was colocalized with the deposition of C5b-9. The results of the present study indicate that complement activation leading to generation of MAC may possibly be involved in the pathogenesis of vascular injury in a significantly large number of skin lesions and of HSP nephritis.