Detection of immune deposits in skin lesions of patients with Wegener's granulomatosis

Abstract

Background-Wegener's granulomatosis (WG) is considered a pauci-immune systemic vasculitis based on the absence of immune deposits in renal biopsies of patients with active disease. In animal models of antineutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis, immune deposits along the glomerular capillary wall are present at early stages of lesion development. These deposits are degraded rapidly, resulting in "pauci-immune" lesions. Objective-To test the hypothesis that immune deposits can also be detected in early lesions of patients with WG, thereby initiating an inflammatory reaction that, in time, is augmented in the presence of ANCA, resulting in pauci-immune lesions later on. Methods-The presence of immune deposits in skin biopsies taken within 48 hours of lesion development was investigated. Direct immunofluorescence was used to examine 32 skin biopsies for the presence of immune deposits (IgG, IgA, IgM, C3c). When possible, a comparison was made between the immunofluorescence findings in renal and skin biopsies taken at the same time. Results-Four of 11 biopsies taken at initial presentation and four of 21 biopsies taken at the onset of a relapse of WG showed IgG and/or IgA containing immune deposits in the subepidermal blood vessels. All nine renal biopsies showed pauci-immune glomerulonephritis, irrespective of the presence (n=5) or absence (n=4) of immune deposits in the skin biopsy. Conclusion-A substantial number of skin biopsies showed immune deposits during active disease. These results could support the hypothesis that immune complexes may trigger vasculitic lesions in WG.

The Immunopathological Spectrum of Crescentic Glomerulonephritis: A Survey of 106 Patients in a Single Chinese Center

“…It was demonstrated in animal models that cellular immunity may interfere with the formation of the immune complex [28]. Other animal experiments and some clinical findings also suggest that AAV with immune-complex deposits may represent an early stage in the disease course [29,30]. …”

Wegener?s Granulomatosis

“…The skin may be an exception to the rule since one study reported cutaneous vascular immune complex deposits. The authors considered these lesions "early" in contrast to the "late" pauci-immune lesions [25].…”

Pathology of the Cutaneous Vasculitides: A Comprehensive Review

“…Patients presenting with LCV are more likely to have concurrent musculoskeletal and renal involvement and a more rapidly progressive disease course when compared to patients without cutaneous manifestations and are more likely to, over time, develop renal, musculoskeletal, and ocular manifestations when compared to patients with granulomatous dermatitis (Barksdale et al, 1995). While direct immunofluorescence typically fails to demonstrate immunoglobulin or complement deposition on renal biopsies, skin biopsies frequently show perivascular deposits of IgG, IgM, IgA, and C3 in subepidermal and dermal vessels (Brons et al, 2001). In patients who have had a relapse of WG, immunoglobulin deposits can be seen along the basement membrane and within the dermis (Brons et al, 2001).…”

“…While direct immunofluorescence typically fails to demonstrate immunoglobulin or complement deposition on renal biopsies, skin biopsies frequently show perivascular deposits of IgG, IgM, IgA, and C3 in subepidermal and dermal vessels (Brons et al, 2001). In patients who have had a relapse of WG, immunoglobulin deposits can be seen along the basement membrane and within the dermis (Brons et al, 2001). …”