Local and systemic activationofthe whole complement cascade in human leukocytoclastic cutaneous vasculitis; C3d,g and terminal complement complex as sensitive markers

Abstract

SUMMARY We have studied complement activation both in plasma samples and In lesional skin from palients with leukocytoclaslic cutaneous vasculitis (LCV). Enzyme immunoassay (EIA) quantification of the complement activation markers. C3d,g and fhe terminal complement complex (TCC) in plasma, showed lhal their levels were significantly increased in 66% and 55% of the patienis, respectively (n = 29) compared with healthy controls, whereas the standard measurements of C3, factor B, Clq, C4and C2 were generally within normal range. Elevations of C3d,g and TCC levels in plasma were signifieantly eorrelated. Importantly, a signifieant correlation was found between the severity of the vasculitis and both C3d,g and TCC plasma levels. Immunofluorescence studies of skin biopsy specimens demonstrated simultaneous presence of peri vascular dermal deposits of C3d,g and TCC in lesional skin from 96 Mi and 80% respectively of the patients (n= 25). There was a significant eorrelation between the intensity of the deposits of bolh markers. Clusterin, a TCC inhibitory protein, was always found at the same sites of perivascular TCC deposits, Immunofluorescence studies at the epidermal basemenl membrane zone (BMZ) revealed in each case deposits of C3d,g which were accompanied by TCC deposits in 52% of the biopsy specimens. These data demonstrate that there is a local and systemic activation of the whole complement cascade in human LCV. The presenee of both C3d,g and clusterin‐associatcd TCC perivascular deposits suggests an intervention of a regulatory mechanism oflocal complement activation in LCV. Einally, measurement of plasma C3d,g and TCC appears to be a sensitive indicator of systemic complement activation and disease severity in LCV.

Injection site reactions after subcutaneous oligonucleotide therapy

“…Complement activation is known to play a key role in dermatological inflammatory conditions . Leucocytoclastic vasculitis has been demonstrated in ISR biopsies of mipomersen‐treated human subjects , which implies the potential involvement of complement, as complement complexes and perivascular complement deposits are commonly observed in this type of vasculitis . Leukocytoclastic vasculitis (also known as hypersensitivity vasculitis/angiitis) is commonly confined to the skin and is caused by vascular damage due to nuclear debris from infiltrating neutrophils.…”

Roflumilast-induced Local Vascular Injury Is Associated with a Coordinated Proteome and Microparticle Change in the Systemic Circulation in Pigs

“…43, No. 4, 2015 NOVEL DIVI BIOMARKERS IN PIGS 577 with a direct implication of Apo J in preventing complement activation in specific types of vasculitides (Dauchel et al 1993). Finally, by flow cytometry analysis, we demonstrate a significant rise in both total and endothelial MPs (annexin V þ and CD105 þ (endoglin)/CD45 À ) in roflumilast-administered animals.…”

Complement Activation in Inflammatory Skin Diseases

“…Moreover, the increased level of C3d and C5b-9 has been shown to correlate with vasculitis activity. Interestingly, circulating C3d and C5b-9 levels did correlate with disease activity but not with the intensity of perivascular cutaneous depositions, suggesting that C3d and C5b-9 plasma levels are caused by systemic complement activation instead of passive diffusion from cutaneous lesions into the circulation ( 86 ).…”