Complement activation in pauci-immune necrotizing and crescentic glomerulonephritis: results of a proteomic analysis

Sethi, Sanjeev; Zand, Ladan; Vriese, An S. De; Specks, Ulrich; Vrana, Julie A.; Kanwar, Siddak S.; Kurtin, Paul J.; Theis, Jason D.; Angioi, Andrea; Cornell, Lynn D.; Fervenza, Fernando C.

doi:10.1093/ndt/gfw299

Cited by 65 publications

(36 citation statements)

References 40 publications

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“…The complement activation products were detected in kidneys of patients with AAV, even in ANCAnegative AAV patients [4][5][6][7]22]. The complement system was regulated strictly in the normal state.…”

Section: Discussionmentioning

confidence: 97%

Complement regulatory proteins in kidneys of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Cheng

Gou

Qiu

et al. 2017

Clinical and Experimental Immunology

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The complement system activation is involved in the development of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The study aimed to investigate the expression of complement regulatory proteins (CRPs) CD46, CD55 and CD59 in kidneys of 51 AVV patients. The expression of CD46, CD55 and CD59 in kidneys was detected by immunohistochemistry and double immunofluorescence staining. The immunohistochemical examination revealed that expression of the three CRPs could be detected in the glomeruli and tubules of both AAV patients and normal controls. The expression levels of the three CRPs in glomeruli of patients with AAV were significantly lower than those of normal controls. The scores of CD46 and CD55 expression in the tubules of AAV patients were significantly lower than those of normal controls, while there was no significant difference between the scores of CD59 expression in tubules of AAV patients and those of normal controls. Among AAV patients, the expression level of CD46 in glomeruli correlated inversely with the proportion of normal glomeruli, while it correlated with tubular atrophy in renal interstitium (r 5 -0Á305, P 5 0Á026; r 5 0Á330, P 5 0Á023, respectively). The expression levels of CD55 and CD59 in glomeruli correlated with the proportion of total crescents (r 5 0Á384, P 5 0Á006; r 5 0Á351, P 5 0Á011, respectively). Double immunofluorescence staining indicated that all three CRPs were expressed on endothelial cells, podocytes and mesangial cells in glomeruli. The expression levels of the three CRPs were dysregulated in kidneys of patients with AAV. The expression levels of CD46, CD55 and CD59 were associated with the severity of renal injury of AAV patients.

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Section: Discussionmentioning

confidence: 97%

Complement regulatory proteins in kidneys of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Cheng

Gou

Qiu

et al. 2017

Clinical and Experimental Immunology

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“…The complement activation system is composed of three pathways: the classical pathway, the alternative pathway, and the MBL pathway. Evidence from in vivo and in vitro studies have suggested that the alternative pathway plays a crucial role in the development of AAV . Sugimoto et al illuminated that polyethylene glycol‐precipitated immune complexes from IgG4‐RD patients could activate both the classical and the MBL pathways, although the mechanism has not been clarified.…”

Section: Discussionmentioning

confidence: 99%

Clinical and pathological features of patients with antineutrophil cytoplasmic antibody‐associated vasculitides concomitant with IgG4‐related disease

Chen

Xü

et al. 2019

Int J of Rheum Dis

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Aim:The characteristics and the pathogenesis of the concomitant antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) and immunoglobulin G4related disease (IgG4-RD) have not been elucidated. Method:We included 92 AAV patients with renal biopsy results. Among them, 10 patients met both AAV and IgG4-RD criteria (concomitant group). The IgG subclasses of myeloperoxidase (MPO)-ANCA in both serum and renal tissue were measured and complement activation components were detected in serum. Results:Patients in the concomitant group had both elevated serum IgG4 levels and positive MPO-ANCA. They had higher levels of eosinophil counts, serum globulin, IgG, IgE and C-reactive protein than patients in the AAV alone group. All 10 patients had glomerulonephritis with crescents and seven patients also had segmental necrosis of the glomerular capillary wall. Most of them also presented with storiform fibrosis and lymphoplasmacytic infiltration in renal interstitium with IgG4 positive plasma cells more than 10/high-power field. Eight patients achieved remission with improved renal function, the other two patients were on maintenance dialysis. The IgG4 subclass of MPO-ANCA was higher in the concomitant group than that in AAV alone group. A merge of IgG4 and MPO immunofluorescence was observed in parts of the mesangium of concomitant AAV and IgG4-RD patients. For complement components, Bb and mannose-binding lectin were elevated in serum of concomitant AAV and IgG4-RD patients. Conclusion:We showed a new overlap syndrome of AAV and IgG4-RD, in which the IgG4 subclass of ANCA may be a pathogenic factor. K E Y W O R D Santineutrophil cytoplasmic antibody, complement, IgG4, IgG4-related disease, vasculitides

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“…Previous studies have shown that the LCMS/MS analysis can be used to detect these amyloid proteins in familial and hereditary amyloidosis, such as transthyretin (ATTR), leukocyte chemotactic factor 2 (LECT2), fibrinogen Aα chain, and apolipoproteinA-I, A-II, and A-IV, which are otherwise difficult to diagnose when using routine pathological techniques [18][19][20]. Moreover, the LCMS/MS proteomic analysis has also been recently utilized to define the glomerular proteomic profile of various types of glomerulonephritis [21,22].…”

Section: Discussionmentioning

confidence: 99%

Optimal conditions and the advantages of using laser microdissection and liquid chromatography tandem mass spectrometry for diagnosing renal amyloidosis

et al. 2018

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Background Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has recently been utilized to accurately detect the amyloid proteins of renal amyloidosis. The present study investigated the optimal procedures for analyzing samples by LCMS/MS, and the advantage of using this technique to diagnosis renal amyloidosis. Methods To detect amyloid proteins, laser microdissected glomeruli from AL (n = 13) or AA (n = 10) renal amyloidosis patients were digested and analyzed by LCMS/MS. To determine the best procedures for analyzing samples by LCMS/MS, we examined the suitability of tissue samples, frozen or formalin-fixed paraffin-embedded (FFPE), the number of dissected glomeruli required for analysis (2, 10, or 50 glomeruli), and the amount of trypsin with or without dithiothreitol (DTT). We additionally compared the detection of amyloid proteins between immunostaining and LCMS/MS. Results Examining 10 dissected glomeruli from FFPE sections digested with trypsin 3 µL (0.1 mg/mL) without DDT made it possible to detect amyloid protein in all 10 AA and in 10 out of 12 AL amyloidosis cases. All AA amyloidosis cases were diagnosed using immunohistochemistry for amyloid A. With immunostaining, however, there were several inconclusive immunoglobulin and/or their light chain staining noted in the AA or AL amyloidosis cases. Even so, LCMS/MS was able to accurately detect amyloid protein in renal amyloidosis. Conclusion The use of 10 laser microdissected glomeruli (170,000-220,000 µm 2 ) with amyloid deposition from FFPE sections digested with trypsin 3 µL (0.1 mg/mL) allowed the accurate detection of amyloid protein in AA and AL amyloidosis.

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Complement activation in pauci-immune necrotizing and crescentic glomerulonephritis: results of a proteomic analysis

Cited by 65 publications

References 40 publications

Complement regulatory proteins in kidneys of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Complement regulatory proteins in kidneys of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Clinical and pathological features of patients with antineutrophil cytoplasmic antibody‐associated vasculitides concomitant with IgG4‐related disease

Optimal conditions and the advantages of using laser microdissection and liquid chromatography tandem mass spectrometry for diagnosing renal amyloidosis

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