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Maryvonne Hourmant - One of the best experts on this subject based on the ideXlab platform.

  • elevated soluble flt1 inhibits endothelial repair in pr3 ANCA Associated Vasculitis
    Journal of The American Society of Nephrology, 2012
    Co-Authors: Sandrine Le Roux, Ruth J Pepper, Alexandre Dufay, Melanie Neel, Emmanuelle Meffray, Noel Lamande, Marie Rimbert, Regis Josien, Mohamed Hamidou, Maryvonne Hourmant
    Abstract:

    Antineutrophil cytoplasmic antibody (ANCA)–Associated Vasculitis exhibits endothelial damage, but the capacity for vessel repair in this disorder is not well understood. Here, we observed a marked increase in serum levels of soluble Flt1 (sFlt1), a potent inhibitor of vascular endothelial growth factor, in patients with active ANCA-Associated Vasculitis compared with patients during remission and other controls. Serum levels of sFlt1 correlated with C5a, an anaphylatoxin released after complement activation. Serum from patients with acute ANCA-Associated Vasculitis disrupted blood flow in the chicken chorioallantoic membrane assay, suggesting an antiangiogenic effect. Preincubation with excess human vascular endothelial growth factor prevented this effect. Anti–proteinase-3 (PR3) mAb and serum containing PR3-ANCA from patients with active Vasculitis both induced a significant and sustained release of sFlt1 from monocytes, whereas anti-myeloperoxidase (MPO) mAb or polyclonal antibodies did not. However, the serum containing polyclonal PR3-ANCA did not induce release of sFlt1 from cultured human umbilical vein endothelial cells. In summary, these data suggest that anti-PR3 antibodies, and to a much lesser extent anti-MPO antibodies, increase sFlt1 during acute ANCA-Associated Vasculitis, leading to an antiangiogenic state that hinders endothelial repair.

  • Elevated Soluble Flt1 Inhibits Endothelial Repair in PR3-ANCA–Associated Vasculitis
    Journal of the American Society of Nephrology : JASN, 2011
    Co-Authors: Sandrine Le Roux, Ruth J Pepper, Alexandre Dufay, Melanie Neel, Emmanuelle Meffray, Noel Lamande, Marie Rimbert, Regis Josien, Mohamed Hamidou, Maryvonne Hourmant
    Abstract:

    Antineutrophil cytoplasmic antibody (ANCA)–Associated Vasculitis exhibits endothelial damage, but the capacity for vessel repair in this disorder is not well understood. Here, we observed a marked increase in serum levels of soluble Flt1 (sFlt1), a potent inhibitor of vascular endothelial growth factor, in patients with active ANCA-Associated Vasculitis compared with patients during remission and other controls. Serum levels of sFlt1 correlated with C5a, an anaphylatoxin released after complement activation. Serum from patients with acute ANCA-Associated Vasculitis disrupted blood flow in the chicken chorioallantoic membrane assay, suggesting an antiangiogenic effect. Preincubation with excess human vascular endothelial growth factor prevented this effect. Anti–proteinase-3 (PR3) mAb and serum containing PR3-ANCA from patients with active Vasculitis both induced a significant and sustained release of sFlt1 from monocytes, whereas anti-myeloperoxidase (MPO) mAb or polyclonal antibodies did not. However, the serum containing polyclonal PR3-ANCA did not induce release of sFlt1 from cultured human umbilical vein endothelial cells. In summary, these data suggest that anti-PR3 antibodies, and to a much lesser extent anti-MPO antibodies, increase sFlt1 during acute ANCA-Associated Vasculitis, leading to an antiangiogenic state that hinders endothelial repair.

Dario Ummarino - One of the best experts on this subject based on the ideXlab platform.

Cees G. M. Kallenberg - One of the best experts on this subject based on the ideXlab platform.

  • Reactivity against Complementary Proteinase-3 Is Not Increased in Patients with PR3-ANCA-Associated Vasculitis
    PloS one, 2011
    Co-Authors: Henko Tadema, Coen A. Stegeman, Cees G. M. Kallenberg, Peter Heeringa
    Abstract:

    The etiology of anti-neutrophil cytoplasmic antibodies (ANCA) Associated vasculitides (AAV) is unknown, but the association between infections and autoimmunity has been studied extensively. In 2004, a novel theory was proposed that could link infection and autoimmunity. This 'theory of autoantigen complementarity' was based on the serendipitous finding of antibodies against complementary-PR3 (cPR3) in patients with PR3-ANCA-Associated Vasculitis. cPR3 demonstrated homology to several bacterial proteins, and it was hypothesized that PR3-ANCA develop in response to anti-cPR3 antibodies, as a consequence of the anti-idiotypic network. These data have not been confirmed in other patient cohorts. We investigated the presence of anti-cPR3 antibodies in a Dutch cohort of PR3-ANCA-Associated Vasculitis patients. Anti-cPR3 reactivity was determined in serum using ELISA. Two separate batches of cPR3 were used to determine reactivity in two separate cohorts of PR3-ANCA-Associated Vasculitis patients. We found that anti-cPR3-reactivity was not increased in our PR3-ANCA-Associated Vasculitis patients, in comparison to control groups. Further research will be necessary to prove the concept of autoantigen complementarity in autoimmune diseases.

  • Pathogenesis of ANCA-Associated Vasculitis, an Update
    Clinical reviews in allergy & immunology, 2011
    Co-Authors: Cees G. M. Kallenberg
    Abstract:

    Clinical observations, including a report of neonatal Vasculitis occurring in a child born from a mother with anti-neutrophil cytoplasmic antibody directed to myeloperoxidase (MPO-ANCA)-Associated Vasculitis, suggest a pathogenic role for ANCA. Such a role is supported by in vitro experimental data showing that ANCA can activate primed neutrophils to the production of reactive oxygen species and lytic enzymes resulting in lysis of endothelial cells. An interplay between neutrophils, the alternative pathway of complement, and MPO-ANCA resulting in systemic Vasculitis including necrotizing glomerulonephritis has clearly been demonstrated in animal models. An in vivo pathogenic role of ANCA directed to proteinase 3 (PR3-ANCA) has, however, not been substantiated. In PR3-ANCA-Associated Vasculitis, granulomatous inflammation points to involvement of cell-mediated immunity. In vitro studies, indeed, suggest that PR3-specific Th17 CD4-positive lymphocytes are operative in lesion development. The triggering role of microbial factors is becoming more clear. In particular Staphylococcus aureus carriage and infection with Gram-negative bacteria could contribute to induction and persistence of ANCA-Associated Vasculitis (AAV). Insight into the pathogenic pathways involved in AAV have opened and will further open new ways to targeted treatment.

  • Influenza vaccination does not result in an increase in relapses in patients with ANCA-Associated Vasculitis
    Nephrology dialysis transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2007
    Co-Authors: P. M. Stassen, Jan Stephan Sanders, Cees G. M. Kallenberg, Coen A. Stegeman
    Abstract:

    Background. Vaccination against influenza has been suggested to induce relapses of ANCA-Associated Vasculitis but evidence is lacking. In this study, we assessed whether vaccination against influenza increases the occurrence of relapses in patients with ANCA-Associated Vasculitis. Methods. Two hundred and thirty consecutive patients with ANCA-Associated Vasculitis from our out-patient clinics of a tertiary referral center, with at least 1 year of follow-up, were included. Retrospectively, the relapse rate per 100 patients at risk in patients who had been vaccinated against influenza within the preceding year and in patients who not had been vaccinated within that time period were calculated. Results. The relapse rate per 100 patients at risk was lower in patients who had been vaccinated against influenza (3.4) than in patients who had not been vaccinated (6.3), when analyzed for the entire year and for every quarter of the year. Also, the disease-free survival per separate year according to the vaccination status was lower in all 5 years in patients who had been vaccinated, being statistically significant in 2 years. Conclusion. Vaccination against influenza does not increase the relapse rate in patients with ANCA-Associated Vasculitis.

Cornelis Kallenberg - One of the best experts on this subject based on the ideXlab platform.

  • pathogenesis of pr3 ANCA Associated Vasculitis
    Journal of Autoimmunity, 2008
    Co-Authors: Cornelis Kallenberg
    Abstract:

    Wegener's Granulomatosis (WG) is closely Associated with antineutrophil cytoplasmic autoantibodies (ANCA), particularly those directed to proteinase 3 (PR3). ANCA directed to myeloperoxidase (MPO) are Associated with microscopic polyangiitis (MPA) and the Churg Strauss syndrome. PR3-ANCA Associated Vasculitis differs from MPO-ANCA Associated Vasculitis particularly in the occurrence of granulomatous inflammation and more widespread disease in the former condition. Studies in experimental animals strongly suggest a pathogenic role for MPO-ANCA, but this is less clear for PR3-ANCA. Here, we review pathogenic pathways in PR3-ANCA Associated Vasculitis focussing on unique patterns of PR3 expression on the neutrophil membrane in WG, as surface expression of PR3 is a prerequisite for stimulation by PR3-ANCA; (PR3-specific) cellular immunity in WG; and the role of Staphylococcus aureus carriage in this disease. These factors, together, may explain, at least in part, differences in clinical expression between MPO-ANCA and PR3-ANCA Associated Vasculitis.

  • The Th1 and Th2 paradigm in ANCA-Associated Vasculitis.
    Kidney & blood pressure research, 2003
    Co-Authors: Jan Stephan Sanders, Coen A. Stegeman, Cornelis Kallenberg
    Abstract:

    In the pathogenesis of anti-neutrophil cytoplasm antibodies (ANCA)-Associated Vasculitis, T cell contribution is indicated by T cell-dependent ANCA production combined with the presence of T cells in inflammatory infiltrates. However, the exact pathogenic role of T cells in ANCA-Associated Vasculitis remains to be determined. The Th1/Th2 concept is useful for understanding T cell involvement in pathological processes. This review focuses on T cells and particularly the Th1/Th2 paradigm in ANCA-Associated Vasculitis. Most research has been done in Wegener's granulomatosis, where a shift in T cell response, from a Th1 pattern in localized disease towards a Th0/Th2 pattern in generalized disease, appears to occur. Although less thoroughly studied, data in Churg-Strauss syndrome and microscopic polyangiitis indicate that these diseases are predominantly Associated with Th2 patterns. Further studies elucidating the true nature of the polarization towards Th1 or Th2 in ANCA-Associated Vasculitis are clearly needed.

Caroline O.s. Savage - One of the best experts on this subject based on the ideXlab platform.

  • Pathogenesis of ANCA-Associated Vasculitis
    Rheumatic diseases clinics of North America, 2010
    Co-Authors: Julia Flint, Matthew D. Morgan, Caroline O.s. Savage
    Abstract:

    Antineutrophil cytoplasm antibody (ANCA)-Associated Vasculitis (AAV) comprises a group of systemic inflammatory vasculitides Associated with circulating autoantibodies directed against the neutrophil granule components proteinase 3 and myeloperoxidase. ANCA interact with their target antigens on cytokine primed neutrophils, causing neutrophil activation via several signaling pathways that culminates in endothelial interaction, degranulation, cytokine production, and endothelial and tissue damage. The presence of autoantibodies implies the assistance of autoreactive T-helper cells and B cells, and a failure of regulatory mechanisms. This article reviews the current evidence for the pathogenic mechanisms culminating in autoantibody production, the effects of ANCA-neutrophil and neutrophil-endothelial interactions, and the mechanisms of tissue damage.

  • Malignancy is increased in ANCA-Associated Vasculitis
    Rheumatology (Oxford England), 2004
    Co-Authors: Tanya Pankhurst, Caroline O.s. Savage, Caroline Gordon, Lorraine Harper
    Abstract:

    Objective. In the light of previous reports of an association between malignancy and renal Vasculitis, we aimed to investigate the association of malignancy in antineutrophil cytoplasmic antibody (ANCA)-Associated Vasculitis, either Wegener's granulomatosis (WG) or microscopic polyangiitis (MPA), and compare it with the general population and disease control groups comprising patients with systemic lupus erythematosus (SLE) or Henoch-Schonlein purpura (HSP). Methods. A retrospective review of 200 consecutive patients with WG or MPA was performed. Malignancies preceding or concurrent with Vasculitis were recorded and the incidence of malignancy was compared with those in a population of 129 patients with HSP, 333 patients with SLE and a normal population in the West Midlands of the UK. Results. Twenty patients had a diagnosis of malignancy, 14 had MPA and six had WG. Patients with ANCA-Associated Vasculitis had an increased risk of malignancy compared with HSP patients, of whom six patients had malignancy (relative risk 0.85, confidence interval 0.69-1.05; P = 0.034), or SLE patients, of whom five patients had malignancy (relative risk 0.31, 95% confidence interval 0.14-0.7; P < 0.0001). The rate of malignancy compared with an age-matched control group was increased in patients with ANCA-Associated Vasculitis and HSP (ANCA-Associated Vasculitis, relative risk 6.02, 95% confidence interval 3.72-9.74; HSP, relative risk 5.25, 95% confidence interval 2.4-11.5). The presence of ANCA was not predictive of malignancy. Conclusion. In conclusion, patients with ANCA-Associated Vasculitis have an increased risk of preceding or concurrent malignancy.