Search

Background. Complement activation plays an important role in the pathophysiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), although it remains unclear which pathway is activated. Whether pauci-immune necrotizing crescentic glomerulonephritis (pauci-immune GN) with negative ANCA serology is part of the spectrum of AAV or a different disease entity is essentially unknown. Methods. We used proteomic analysis to delineate the complement profile in a series of 13 kidney biopsies of patients with pauci-immune GN, with either proteinase 3 (PR3) (five patients) or myeloperoxidase (MPO) antibodies (four patients) or with consistently negative ANCA serology (four patients). Immunofluorescence staining of glomeruli was essentially negative in the PR3-ANCA and MPO-ANCA groups, while a mild staining for C3 was seen in the ANCA-negative cases. No electron-dense deposits were found in the PR3-ANCA and MPO-ANCA groups, but mesangial and few subepithelial deposits were clearly present in the ANCA-negative specimens. Results. Mass spectrometry revealed low spectra numbers for C3 and immunoglobulins in both PR3-positive and MPOpositive patients with minimal or no C4 and C9. In contrast, larger spectra numbers for C3, moderate spectra numbers for C9, complement factor H-related protein-1 and low spectra numbers for C4, C5 and immunoglobulins were found in the ANCA-negative cases. Conclusion. While complement activation is noted in AAV, the complement activation appears to be more prominent in the ANCA-negative glomerulonephritis. The larger amount of C3 and moderate amount of C9 in the ANCA-negative glomerulonephritis implies activation of the alternate and terminal pathway of complement, suggesting that this entity may be caused or promoted by a genetic or acquired defect in the alternative pathway. [ABSTRACT FROM AUTHOR]

Objectives: The issue of levamisole-adulterated cocaine is emerging as a rapidly growing public health concern due to an increasing number of reports describing its role in cutaneous vasculitis and agranulocytosis. Of note, levamisole is recognized as a contaminant in 69% of the cocaine used within the United States. Methods: We describe a patient who was a chronic cocaine user and developed systemic vasculitis characterized by polyarthralgia, bullous skin lesions, agranulocytosis, and antineutrophil cytoplasmic antibody--positive rapidly progressive glomerulonephritis. Results: The skin biopsy specimen demonstrated leukocyto-clastic vasculitis. The renal biopsy specimen revealed pauci-immune necrotizing and crescentic glomerulonephritis and unusual deposits with medium electron density composed of granules, microspherules, and rare single fibrils on electron microscopy. Conclusions: The electron microscopic features of levami-sole-adulterated cocaine toxicity are novel findings that are presented for the first time, to our knowledge, in this report. [ABSTRACT FROM AUTHOR]

Background. Accumulating evidence supports the notion that the pathogenesis of severe lupus glomerulonephritis is multifactorial and not solely an immune complex-mediated glomerular disease. Alternate mechanisms for glomerular destruction may exist. [ABSTRACT FROM PUBLISHER]

Wegener’s granulomatosis is an ANCA-associated small vessel vasculitis. Because histologically immune complex deposits are frequently lacking, the term pauci-immune has been introduced for this subgroup. We report a patient with fulminant, severe PR3-ANCA-positive Wegener’s granulomatosis and multi-organ involvement (upper respiratory tract, lung, kidneys, skin and general symptoms), who showed pronounced immunoglobulin and complement deposits within the skin biopsy. Our observation supports the hypothesis that immune complex deposits may be under-recognized in early lesions of ANCA-associated Wegener’s granulomatosis. [ABSTRACT FROM PUBLISHER]