Elastase-ANCA-associated idiopathic necrotizing crescentic glomerulonephritis--a report of three cases

Seidowsky, Alexandre; Hoffmann, Maxime; Ruben-Duval, Sophie; Mesbah, Rafik; Masy, E.; Kyndt, X.; Maouad, Béchir; Billion, Stéphane; Noël, Laure Hélène; Vanhille, Philippe; Bataille, Pierre

doi:10.1093/ndt/gfm169

Cited by 10 publications

(4 citation statements)

References 8 publications

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“…Indeed, staining of NETs from PMA-activated neutrophils with anti-MPO antibodies showed the co-localization of MPO and NET-DNA fibers (Figure 5A), whereas anti-PR3-antibodies targeted the cell bodies of netting neutrophils (Figure 5B). Additional known antigens of P-ANCAs are LF (15) and NE (16, 17). Staining with specific antibodies against LF and NE showed that both enzymes are present in NETs (Figures 5C,D), confirming previous reports (1).…”

Section: Resultsmentioning

confidence: 99%

Neutrophil Extracellular Traps Contain Selected Antigens of Anti-Neutrophil Cytoplasmic Antibodies

et al. 2017

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Neutrophil extracellular traps (NETs) are chromatin filaments decorated with enzymes from neutrophil cytoplasmic granules. Anti-neutrophil cytoplasmic antibodies (ANCAs) bind to enzymes from neutrophil cytoplasmic granules and are biomarkers for the diagnosis of systemic vasculitides. ANCA diagnostics are based on indirect immunofluorescence (IIF) of ethanol-fixed neutrophils. IIF shows a cytoplasmic staining pattern (C-ANCA) due to autoantibodies against proteinase 3 (PR3) or a perinuclear staining pattern (P-ANCA) due to autoantibodies against myeloperoxidase (MPO). The distinct ANCA-staining patterns are an artifact of ethanol fixation. Here, we tested NETs as a substrate for the detection of ANCAs in human sera. We observed that P-ANCAs specifically stained NETs, while C-ANCAs targeted the cell bodies of netting neutrophils. The distinct ANCA-staining patterns were caused by the presence of MPO, but not PR3, in NETs. Using NETs as a substrate for IIF, we characterized ANCAs in sera of patients with ANCA-associated vasculitis (AAV). Furthermore, we inhibited serine proteases by diisopropylfluorophosphate to prevent chromatin unfolding and the release of NETs and thus generated neutrophils with MPO-positive nuclei and PR3-positive cytoplasm, which resembled the appearance of ethanol-fixed neutrophils. In conclusion, our data suggest that NETs are selectively loaded with antigens recognized by P-ANCAs, and netting neutrophils provide a physiological substrate for ANCA detection in patients with AAV.

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Section: Resultsmentioning

confidence: 99%

Neutrophil Extracellular Traps Contain Selected Antigens of Anti-Neutrophil Cytoplasmic Antibodies

et al. 2017

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“…Importantly, their study demonstrated that ANCA reactivity was not observed in sera, emphasizing the importance of investigations in the affected tissue [28]. Additional studies support the existence of ANCA/autoantigens in MPO/PR3-ANCA-negative vasculitides including identification of elastase-ANCA in adult ANCA-negative glomerulonephritis [29] and the presence of alpha-enolase, a potential cytosolic autoantigen, in 82% of adults with predominantly ANCA-negative EGPA [30].…”

Section: Discussionmentioning

confidence: 97%

Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels

Akbaba,

Toor,

Mann

et al. 2024

IJMS

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Chronic primary systemic vasculitis (PSV) comprises a group of heterogeneous diseases that are broadly classified by affected blood vessel size, clinical traits and the presence (or absence) of anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3) and myeloperoxidase (MPO). In small vessel vasculitis (SVV), ANCA are not present in all patients, and they are rarely detected in patients with vasculitis involving medium (MVV) and large (LVV) blood vessels. Some studies have demonstrated that lysosome-associated membrane protein-2 (LAMP-2/CD107b) is a target of ANCA in SVV, but its presence and prognostic value in childhood MVV and LVV is not known. This study utilized retrospective sera and clinical data obtained from 90 children and adolescents with chronic PSV affecting small (SVV, n = 53), medium (MVV, n = 16), and large (LVV, n = 21) blood vessels. LAMP-2-ANCA were measured in time-of-diagnosis sera using a custom electrochemiluminescence assay. The threshold for seropositivity was established in a comparator cohort of patients with systemic autoinflammatory disease. The proportion of LAMP-2-ANCA-seropositive individuals and sera concentrations of LAMP-2-ANCA were assessed for associations with overall and organ-specific disease activity at diagnosis and one-year follow up. This study demonstrated a greater time-of-diagnosis prevalence and sera concentration of LAMP-2-ANCA in MVV (52.9% seropositive) and LVV (76.2%) compared to SVV (45.3%). Further, LAMP-2-ANCA-seropositive individuals had significantly lower overall, but not organ-specific, disease activity at diagnosis. This did not, however, result in a greater reduction in disease activity or the likelihood of achieving inactive disease one-year after diagnosis. The results of this study demonstrate particularly high prevalence and concentration of LAMP-2-ANCA in chronic PSV that affects large blood vessels and is seronegative for traditional ANCA. Our findings invite reconsideration of roles for autoantigens other than MPO and PR3 in pediatric vasculitis, particularly in medium- and large-sized blood vessels.

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“…Wiesner et al reported that human neutrophil elastase antibodies (HNE-ANCA) are often found in cocaine-induced midline destructive lesions [ 5 ]. Seidowsky et al reported three cases that developed HNE-ANCA-associated vasculitis with rapidly progressive glomerulonephritis [ 6 ]. Interestingly, both of these reports also had ANCAs for bactericidal-/permeability-increasing protein (BPI), as observed in our case.…”

Section: Discussionmentioning

confidence: 99%

A Case of Concurrent MPO-/PR3-Negative ANCA-Associated Glomerulonephritis and Membranous Glomerulopathy

Nakada

Tsuboi

Takahashi

et al. 2015

Case Reports in Nephrology

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We report a case in which antineutrophil cytoplasmic antibody- (ANCA-) associated glomerulonephritis and membranous glomerulopathy (MGN) were detected concurrently. The patient showed rapidly progressive renal deterioration. A renal biopsy showed crescentic glomerulonephritis, together with marked thickening and spike and bubbling formations in the glomerular basement membranes. Indirect immunofluorescence examination of the patient's neutrophils showed a perinuclear pattern. Enzyme-linked immunosorbent assays revealed that the ANCA in this case did not target myeloperoxidase (MPO) or proteinase 3 (PR3) but bactericidal-/permeability-increasing protein, elastase, and lysosome. The relationship between these two etiologically distinct entities, MPO-/PR3-negative ANCA-associated glomerulonephritis and MGN, remains unclear.

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Elastase-ANCA-associated idiopathic necrotizing crescentic glomerulonephritis--a report of three cases

Cited by 10 publications

References 8 publications

Neutrophil Extracellular Traps Contain Selected Antigens of Anti-Neutrophil Cytoplasmic Antibodies

Neutrophil Extracellular Traps Contain Selected Antigens of Anti-Neutrophil Cytoplasmic Antibodies

Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels

A Case of Concurrent MPO-/PR3-Negative ANCA-Associated Glomerulonephritis and Membranous Glomerulopathy

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