Pathogenesis of ANCA-associated vasculitides

Kallenberg, Cees G. M.

doi:10.1136/ard.2010.138024

Cited by 141 publications

(92 citation statements)

References 46 publications

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“…Among the MPO-AAV patients, MPA accounted for 97%, with 3 patients diagnosed with GPA [PR3-ANCA (-)]; MPO-ANCA may also be present in some of the patients with GPA (Kallenberg, 2011). Previous studies have reported that there was a stronger correlation between PR3-ANCA and the disease activity of AAV (BVAS), while the relationship between MPO-ANCA and BVAS was not consistent with the previous report.…”

Section: Discussionmentioning

confidence: 67%

Clinical analysis of patients with myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis

Shuai

Zhang

et al. 2015

Genet. Mol. Res.

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ABSTRACT. This prospective study analyzed the clinical characteristics of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis and explored the relationship between MPO-ANCA and clinical manifestations of the associated vasculitis in 132 p-ANCA and MPO-ANCA-positive patients (average age, 62.3 ± 14.8 years) who were initially diagnosed with ANCA-associated vasculitis. The p-ANCA and MPO-ANCA levels in peripheral blood were detected in all patients. Among these, 128 (97%) had microscopic polyangiitis (MPA), 3 (2.3%) had granulomatous polyangiitis, and 1 (0.7%) had eosinophilic granulomatous vasculitis. The average time of diagnosis was 10.2 ± 18 months; only 14 (10.6%) patients were diagnosed within 1 month. The main organs involved and the corresponding number of patients were: renal, 95 (72%); lung, 89 (67.4%); joints, 35 (26.5%); heart, 26 (19.7%); peripheral nerve, 23 (17.4%); skin rash, 14 (10.6%); and CNS, 13 (9.8%). Older patients were more likely to show lung involvement in the early disease stage, whereas the joints were involved mostly in the younger patients. The p-ANCA levels (mean titers, 1:60) were not correlated with disease activity and extent of organ (2015) involvement, and the MPO-ANCA levels were positively correlated with disease activity, but had no correlation with the extent of organ involvement. MPO-ANCA vasculitis is a common occurrence in China; it mainly involves the elderly and presents as clinical manifestations of MPA. However, the multiple organ damage is not specific leading to delay in diagnosis. MPO-ANCA may play a pathogenic role in the associated vasculitis, and the diverse clinical manifestations might be related with the different characteristics of MPO-ANCA.

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Section: Discussionmentioning

confidence: 67%

Clinical analysis of patients with myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis

Shuai

Zhang

et al. 2015

Genet. Mol. Res.

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“…The leukocyte-enriched cell suspension was aspirated from the Percoll interface. After the erythrocytes had been removed using lysis solution (139 mM NH 4 Cl and 19 mM Tris), cells were washed with HBSS and resuspended in FCS-containing buffer. Cell viability was assessed by trypan blue staining before flow cytometry or cell transfer experiments.…”

Section: Isolation Of Leukocytes From the Kidney And Spleenmentioning

confidence: 99%

CC Chemokine Ligand 18 in ANCA-Associated Crescentic GN

Brix¹,

Stege²,

Disteldorf³

et al. 2015

Journal of the American Society of Nephrology

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ANCA-associated vasculitis is the most frequent cause of crescentic GN. To define new molecular and/or cellular biomarkers of this disease in the kidney, we performed microarray analyses of renal biopsy samples from patients with ANCA-associated crescentic GN. Expression profiles were correlated with clinical data in a prospective study of patients with renal ANCA disease. CC chemokine ligand 18 (CCL18), acting through CC chemokine receptor 8 (CCR8) on mononuclear cells, was identified as the most upregulated chemotactic cytokine in patients with newly diagnosed ANCA-associated crescentic GN. Macrophages and myeloid dendritic cells in the kidney were detected as CCL18-producing cells. The density of CCL18 + cells correlated with crescent formation, interstitial inflammation, and impairment of renal function. CCL18 protein levels were higher in sera of patients with renal ANCA disease compared with those in sera of patients with other forms of crescentic GN. CCL18 serum levels were higher in patients who suffered from ANCA-associated renal relapses compared with those in patients who remained in remission. Using a murine model of crescentic GN, we explored the effects of the CCL18 murine functional analog CCL8 and its receptor CCR8 on kidney function and morphology. Compared with wild-type mice, Ccr8 2/2 mice had significantly less infiltration of pathogenic mononuclear phagocytes. Furthermore, Ccr8 2/2 mice maintained renal function better and had reduced renal tissue injury. In summary, our data indicate that CCL18 drives renal inflammation through CCR8-expressing cells and could serve as a biomarker for disease activity and renal relapse in ANCA-associated crescentic GN.

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“…Briefly, ANCA produced from auto-reactive B cells activate primed neutrophils and activated neutrophils produce reactive oxygen species and release their lytic contents, initiating vasculitis. Even low doses of pro-inflammatory cytokines, including TNF-alpha, interleukin-(IL) 1 and IL-18, may fuel the inflammation by priming neutrophils and increase their surface expression of ANCA antigens [21].…”

Section: Discussionmentioning

confidence: 99%

Serum ferritin as an activity marker for granulamotosis with polyangiitis

et al. 2017

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Background: Serum ferritin correlates well with the activities of systemic lupus erythematosus (SLE) and dermatomyositis, but it has not been previously studied in patients with vasculitis. Methods: Medical records of granulomatosis with polyangiitis (GPA, Wegener's granulomatosis) patients with at least six months of regular follow-up were evaluated. The activity of GPA was assessed with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG). Serum ferritin and other acute phase markers were measured at initial presentation. Results: Serum ferritin levels were found to be the highest in GPA patients with alveolar hemorrhage, median (IQR) 1041 (1281) lg/L. Patients with renal disease also had high levels of ferritin and it was correlated with concurrent glomerular filtration rate (r ¼ À0.65, p < .001). Serum ferritin is also correlated well with the BVAS/WG scores (r ¼ 0.79, p < .001). Conclusions: Measurement of serum ferritin might help in assessing disease activity of GPA.

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Pathogenesis of ANCA-associated vasculitides

Cited by 141 publications

References 46 publications

Clinical analysis of patients with myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis

Clinical analysis of patients with myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis

CC Chemokine Ligand 18 in ANCA-Associated Crescentic GN

Serum ferritin as an activity marker for granulamotosis with polyangiitis

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