Influence of disease manifestation and antineutrophil cytoplasmic antibody titer on the response to pulse cyclophosphamide therapy in patients with wegener's granulomatosis

Reinhold‐Keller, E.; Kekow, Jörn; Schnabel, A; Schmitt, Wilhelm H.; Heller, Martin; Beigel, A.; Duncker, G.; Gross, Wolfgang L.

doi:10.1002/art.1780370622

Cited by 166 publications

(92 citation statements)

References 18 publications

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“…Pulse cyclophosphamide therapy appears to have good effects in adjuvant treatment of neurosarcoidosis (30). In multi-organ involvement of Wegener granulomatosis (WG) continuous cyclophosphamide treatment seems to have an advantage over intermittent therapy (12). However, a new multi-centre study demonstrated similar effectiveness, inducing first remission in generalised WG by both modalities of cyclophosphamide therapy (31).…”

Section: Discussionmentioning

confidence: 99%

Five cases with central diabetes insipidus and hypogonadism as first presentation of neurosarcoidosis

et al. 2000

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Objectives: We retrospectively reviewed 5 patients with neurosarcoidosis, who all presented with central diabetes insipidus and hypogonadism. Design: This was a single-centre, retrospective analysis of 5 cases with a minimum follow-up of 2 years. Methods: Case analysis included clinical, biochemical, and endocrinological evaluation and frequent CT/MRI scans of involved organs as primary evaluation and in response to immunosuppressive therapy. Result: Neurosarcoidosis was diagnosed in all patients. Two patients had no proven extracerebral manifestation and had a stable disease over 3 and 5 years. One patient showed deterioration with corticosteroids alone but partial remission after additional cyclophosphamide. Pituitary dysfunction remained unchanged in all patients, despite total clinical and radiological remission in two patients. However, one of these patients died of acute granulomatous meningoencephalitis after two years of follow-up. Conclusion: Although the presenting symptoms of neurosarcoidosis may vary, the occurrence of central diabetes insipidus associated with typical radiological features is suggestive of neurosarcoidosis. However, there is an increasing number of case reports on lymphocytic hypophysitis. Without the bioptic diagnosis, the differentiation between potentially lethal isolated neurosarcoidosis and lymphocytic hypophysitis is difficult. These cases demonstrate the difficulties in diagnosing neurosarcoidosis and reflect experiences with follow-up parameters.

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Section: Discussionmentioning

confidence: 99%

Five cases with central diabetes insipidus and hypogonadism as first presentation of neurosarcoidosis

et al. 2000

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“…First, TGF-overexpression is associated with cellular and humoral immunodeficiency [21,23]. In SV, infectious disease shows a high prevalence, in which TGF-may account, together with other factors including immunosuppression by therapy, for a high mortality rate [28]. Second, TGF-overexpression has been shown to be a tumour-promoting factor [29].…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor-beta (TGF-β) expression and interaction with proteinase 3 (PR3) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Csernok

Szymkowiak

Mistry

et al. 1996

Clinical and Experimental Immunology

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SUMMARYTGF-¯is a multifunctional cytokine modulating the onset and course of autoimmune diseases as shown in experimental models. The aim of this study was to investigate TGF-¯expression in ANCA-associated vasculitis (AAV), and the possible interactions of this cytokine with lysosomal enzymes identified as ANCA autoantigens (e.g. PR3). This included TGF-¯effects on the translocation of the lysosomal enzymes to the cell surface of polymorphonuclear neutrophils (PMN), and the presumed activation of non-bioactive, latent TGF-¯by these enzymes. Patients with various types of systemic vasculitis (SV) were studied, including three different types of AAV (Wegener's granulomatosis (WG), Churg-Strauß syndrome (CSS) and microscopic polyangiitis (MPA)). Regardless of the type of assay applied, the TGF-¯1 isoform was found to be overexpressed in SV, including AAV, and to correlate with disease activity as shown for WG. Mean TGF-¯1 plasma levels in AAV patients ranged from 8 . 9 ng/ml (WG) to 13 . 3 ng/ml (CSS) (control 4 . 2 ng/ml; P < 0 . 01), while TGF-¯2 levels were not elevated. Flow cytometry analysis showed TGF-¯1 to be a potent translocation factor for PR3 comparable to other neutrophilactivating factors such as IL-8. PR3 membrane expression on primed PMN increased by up to 51% after incubation with TGF-¯1. PR3 itself was revealed as a potent activator of latent TGF-¯, thus mediating bioeffects of this cytokine. These findings, together with other features of TGF-¯such as induction of angiogenesis and its strong chemotactic capacity, indicate that TGF-¯might serve as a proinflammatory factor in SV, especially in AAV.

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“…The nature ofthe data collection for BVAS and VDI allows weighting to be subsequently applied to the scores as well as the derivation of other activity indiced such as the Disease Extension Index [6]. Patient function will be scored using the Short Form 36 {SF-36) questionnaire from the Medical Outcomes Trust; an existing, validated, score available in several European languages [7]. Adverse drug reactions are recorded in a standardised form which assesses the severity and consequences of the reaction and is complimented by a glossary of definitions of the more frequent adverse effects.…”

Section: Pementioning

confidence: 99%

European therapeutic trials in ANCA-associated systemic vasculitis: disease scoring, consensus regimens and proposed clinical trials EUROPEAN COMMUNITY STUDY GROUP ON CLINICAL TRIALS IN SYSTEMIC VASCULITIS ECSYSVASTRIAL (BMHl-Cr93-1078)

Rasmussen¹,

Jayne²,

Abramowicz³

et al. 1995

Clinical and Experimental Immunology

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In previous phases of this project, proteinase 3 (PR3) and myeloperoxidase (MPO), the main antigenic target molecules of antineutrophil cytopiasmic antibodies, were isolated and applied in standardized ELISAs.In this study, standardized ELISAs with three PR3 preparations (from Copenhagen (CO), Raisdorf (RS) and Leiden (LF)) and one MPO preparation (from Copenhagen), were evaluated in a large retro-and prospective clitiical study.New patients (n=174) with primary systemic vasculitis (Wegener's granulomatosis, microscopic polyangiitis and idiopathic rapidly progressive glomerulonephritis, classical PAN and Churg-Strauss Syndrome) were included. Retrospectively, another 190 patients were evaluated. Furthermore control sera were obtained from patients with other forms of vasculitis, glomerulonephritis or granulomatous diseases (disease controls, n = 184) and healthy donors (healthy controls, n = 728). All patients were categorized by a system based on clinical and histoiogical data. Patients were followed up for at least 1 year after diagnosis in order to evaluate a possible correlation between ANCA levels and disease activity.The sensitivity of the anti-PR3 assays for histologically proven WG was between 59% and 69% in new patients, with a sensitivity of 22% for the anti-MPO assay. Similar figures were found for patients with clinically suspected WG. This was comparable with the results of the IIF test. In MPA and IRPGN a larger percentage of patients had anti-MPO antibodies than in WG. Only a few patients with PAN and CSS were investigated, and most of these were negative in the ELISAs.The specificity ofthe assays for disease controls was 89-91% for the anti-PR3 assays and 95% for the anti-MPO assay. In the healthy controls the specificity was 98-99%. The specificity of the IIF test was 97% for a cANCA pattern and 81 % for a pANCA pattern in disease controls. The combination of cANCA with anti-PR3 and pANCA with anti-MPO both had a specificity of 99%.Further details will be presented during the meeting, in addition to the results of a follow-up study with correlation ofdisease activity and ANCA level. From this study we can conclude that ELISAs using purified PR3 or MPO are not more sensitive than the IIF test. However, the anti-MPO assay is more specific for systemic vascuitis as compared to disease controls with related diseases. Furthermore, the combination of the IIF test with antigen-specific ELISAs is very specific for the diagnosis Wegetier's granulomatosis, microscopic polyangiitis and idiopathic rapidly progressive gtomerulonephritis.

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Influence of disease manifestation and antineutrophil cytoplasmic antibody titer on the response to pulse cyclophosphamide therapy in patients with wegener's granulomatosis

Cited by 166 publications

References 18 publications

Five cases with central diabetes insipidus and hypogonadism as first presentation of neurosarcoidosis

Five cases with central diabetes insipidus and hypogonadism as first presentation of neurosarcoidosis

Transforming growth factor-beta (TGF-β) expression and interaction with proteinase 3 (PR3) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

European therapeutic trials in ANCA-associated systemic vasculitis: disease scoring, consensus regimens and proposed clinical trials EUROPEAN COMMUNITY STUDY GROUP ON CLINICAL TRIALS IN SYSTEMIC VASCULITIS ECSYSVASTRIAL (BMHl-Cr93-1078)

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