Proteinase-3 mRNA expressed by glomerular epithelial cells correlates with crescent formation in Wegener's granulomatosis

Proteinase-3 mRNA expressed by glomerular epithelial cells correlates with crescent formation in Wegener's granulomatosis. Background Wegener's granulomatosis (WG) is characterized by systemic vasculitis with crescentic glomerulonephritis (CGN) and circulating autoantibodies directed against neutrophil cytoplasmic antigens (ANCA). Proteinase 3 (PR-3), a neutral serine proteinase in neutrophils implicated in the growth control of myeloid cells, has been identified as the target antigen for ANCA in WG. Since the kidneys are frequently involved in WG, we studied the in situ expression of PR-3 by renal parenchymal cells. Methods We assessed the expression of PR-3 in kidney biopsies of 15 patien…

Correlation of renal tubular epithelial cell-derived interleukin-18 up-regulation with disease activity in MRL-Faslpr mice with autoimmune lupus nephritis.

Objective MRL-Faslpr mice spontaneously develop an autoimmune disease that mimics systemic lupus erythematosus in humans. Infiltrating T cells expressing interferon-γ (IFNγ) are responsible for the autoimmune kidney destruction in MRL-Faslpr mice, and interleukin-18 (IL-18) released by mononuclear phagocytes stimulates T cells to produce the IFNγ. Since MRL-Faslpr T cells are characterized by an overexpression of the IL-18 receptor accessory chain, we sought to determine the impact of IL-18 on the progression of lupus nephritis in MRL-Faslpr mice. Methods IL-18 expression in sera and kidney tissues from MRL-Faslpr mice was determined by enzyme-linked immunosorbent assay (ELISA), reverse tra…

In vitro production of anti-neutrophilocyte-cytoplasm-antibodies (ANCA) by Epstein-Barr virus-transformed B-cell lines in Wegener's granulomatosis.

The frequent detection of anti-neutrophilocyte-cytoplasm-antibodies (ANCA) in patients with Wegener's granulomatosis (WG) led to the supposition that this disease might be of autoimmune nature. For some authors assume that Epstein-Barr virus (EBV) infection of human B-lymphocytes besides polyclonal activation could reveal the cryptic immune status against different autoantigens in patients with autoimmune diseases we investigated EBV-transformed B-lymphocytes from patients with Sjögren's syndrome, mixed connective tissue disease, WG and healthy blood donors. Two stable B-cell lines (Ho3, We1) could be established. Inhibition experiments showed that antibodies produced by transformed B-lymph…

Neue Therapiekonzepte bei Morbus Wegener

Drug-induced hepatitis: a rare complication of oral anticoagulants.

Hepatotoxicity is a rare complication of coumarin anticoagulants. We present the case of a 56-year-old woman who developed a viral-hepatitis-like picture 8 months after mitral valve replacement and oral anticoagulation. Phenprocoumon-induced hepatitis was diagnosed after positive reexposure and improvement following withdrawal of the drug. There appeared to be cross-reactivity to warfarin since this drug led to a similar increase in alkaline phosphatase and gamma-glutamyl transferase after a few days of administration. Liver biopsy showed an acute viral-hepatitis-like picture. Anticoagulation was changed to a subcutaneous low molecular weight heparin and low-dose aspirin. Because of the wid…

Vasculitic wallenberg syndrome with detection of anti-proteinase 3 antibodies in the cerebrospinal fluid of a patient with severe Wegener's granulomatosis and only mild kidney involvement.

Synovial fluid-derivedYersinia-reactive T cells responding to human 65-kDa heat-shock protein and heat-stressed antigen-presenting cells

Humoral and cellular immune reactions to heat-shock proteins have been implicated in the pathogenesis of arthritis. Heat-shock proteins occur in bacteria as well as all eukaryotes and have been highly conserved during evolution. Cross-reactivity between bacterial and human heat-shock proteins induced at the site of inflammation may underlie the pathogenesis of some forms of arthritis. In order to test this hypothesis, we raised and cloned a Yersinia-specific T cell line from the synovial fluid lymphocytes of a patient with Yersinia-induced reactive arthritis. From this line we obtained a CD4+ T cell clone that proliferated in response to Yersinia antigens and both to the mycobacterial and t…

Complete congenital heart block in autoimmune hepatitis (SLA-positive).

Complete congenital heart block is a serious complication of neonatal lupus erythematosus which most often occurs in children of mothers suffering from connective tissue disease. We report the occurrence of complete congenital heart block associated with autoimmune hepatitis (SLA-positive). A 32-year-old woman was treated for more than 10 years for autoimmune hepatitis (SLA-/ANA-positive) and remained in clinical remission under immunosuppressive therapy. She showed an MHC-haplotype typical for autoimmune hepatitis (A1, B8, DR3). After a normal first pregnancy, an emergency caesarean section was performed in the 32nd week of her second pregnancy because of fetal bradycardia. The child died …