Distribution of the granulocyte serine proteinases proteinase 3 and elastase in human glomerulonephritis

Mrowka, Christian; Csernok, Elena; Gross, Wolfgang L.; Feucht, Helmut E.; Bechtel, Ulrike; Thoenes, G. H.

doi:10.1016/0272-6386(95)90006-3

Cited by 25 publications

(15 citation statements)

References 20 publications

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“…Without inhibition, proteinase 3 and elastase are capable of inducing endothelial cell apoptosis and cytokine and tissue factor production (39 -41). Moreover proteinase 3 and elastase have been shown in kidney biopsies of ANCAassociated pauci-immune necrotizing vasculitis (42), and elevated levels of proteinase 3 and elastase could be demonstrated in patients with ANCA-associated vasculitis (43,44). Thus these results point to a role of ␣ 1 -antitrypsin as a mediator of activity in ANCA-associated vasculitis.…”

Section: Discussionmentioning

confidence: 71%

Identification and Validation of Urinary Biomarkers for Differential Diagnosis and Evaluation of Therapeutic Intervention in Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis

Haubitz

Good

Woywodt

et al. 2009

Molecular & Cellular Proteomics

102

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Renal activity and smoldering disease is difficult to assess in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) because of renal scarring. Even repeated biopsies suffer from sampling errors in this focal disease especially in patients with chronic renal insufficiency. We applied capillary electrophoresis coupled to mass spectrometry toward urine samples from patients with active renal AAV to identify and validate urinary biomarkers that enable differential diagnosis of disease and assessment of disease activity. The data were compared with healthy individuals, patients with other renal and non-renal diseases, and patients with AAV in remission. 113 potential biomarkers were identified that differed significantly between active renal AAV and healthy individuals and patients with other chronic renal diseases. Of these, 58 could be sequenced. Sensitivity and specificity of models based on 18 sequenced biomarkers were validated using blinded urine samples of 40 patients with different renal diseases. Discrimination of AAV from other renal diseases in blinded samples was possible with 90% sensitivity and 86.7-90% specificity depending on the model. 10 patients with active AAV were followed for 6 months after initiation of treatment. Immunosuppressive therapy led to a change of the proteome toward "remission.

show abstract

Section: Discussionmentioning

confidence: 71%

Identification and Validation of Urinary Biomarkers for Differential Diagnosis and Evaluation of Therapeutic Intervention in Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis

Haubitz

Good

Woywodt

et al. 2009

Molecular & Cellular Proteomics

102

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“…A number of publications demonstrated that at sites of inflammation increased amounts of PR3 or HLE are detected in the extracellular space in patients with WG. 9,32,33 Here, we extend the role of proteases in DCs by showing that PR3 can induce human DC development. We found that PR3 induces phenotypic and functional maturation of a fraction of DCs.…”

Section: Discussionmentioning

confidence: 77%

Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway

Csernok

Gross

et al. 2006

Blood

Self Cite

102

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Autoantibodies to proteinase 3 (PR3) are involved in the pathogenesis of autoimmune-mediated vasculitis in Wegener granulomatosis (WG). To address the question how the autoantigen PR3 becomes a target of adaptive immunity, we investigated the effect of PR3 on immature dendritic cells (iDCs) in patients with WG, healthy blood donors, and patients with Crohn disease (CD), another granulomatous disease. PR3 induces phenotypic and functional maturation of a fraction of blood monocyte-derived iDCs. PR3-treated DCs express high levels of CD83, a DC-restricted marker of maturation, CD80 and CD86, and HLA-DR. Furthermore, the DCs become fully competent antigen-presenting cells and can induce stimulation of PR3-specific CD4+ T cells, which produce IFN-γ. PR3-maturated DCs derived from WG patients induce a higher IFN-γ response of PR3-specific CD4+ T cells compared with patients with CD and healthy controls. The maturation of DCs mediated through PR3 was inhibited by a serine protease inhibitor, by antibodies directed against the protease-activated receptor-2 (PAR-2), and by inhibition of phospholipase C, suggesting that the interactions of PR3 with PAR-2 are involved in the induction of DC maturation. Wegener autoantigen interacts with a “gateway” receptor (PAR-2) on iDCs in vitro triggering their maturation and licenses them for a T helper 1 (Th1)–type response potentially favoring granuloma formation in WG.

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“…Neutrophil-unique proteins cannot be identified in normal renal tissue. However, in glomerulonephritic conditions that are associated with neutrophilic infiltrates, PR3 and other proteinases (e.g., MPO and elastase) can be found within glomeruli, crescents, and tubular epithelial cells (151,172).…”

Section: Potential Pathogenetic Role Of Ancamentioning

confidence: 99%

Antineutrophil cytoplasmic antibodies

Hoffman

Specks

1998

Arthritis & Rheumatism

375

148

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Distribution of the granulocyte serine proteinases proteinase 3 and elastase in human glomerulonephritis

Cited by 25 publications

References 20 publications

Identification and Validation of Urinary Biomarkers for Differential Diagnosis and Evaluation of Therapeutic Intervention in Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis

Identification and Validation of Urinary Biomarkers for Differential Diagnosis and Evaluation of Therapeutic Intervention in Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis

Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway

Antineutrophil cytoplasmic antibodies

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