Susanne Schinke

Publications of Susanne Schinke

• Prospective long-term follow-up of patients with localised Wegener's granulomatosis: does it occur as persistent disease stage?

  Authors: Julia U Holle, Wolfgang L Gross, Konstanze Holl-Ulrich, Petra Ambrosch, Bernhard Noelle, Marcus Both, Elena Csernok, Frank Moosig, Susanne Schinke, Eva Reinhold-Keller

  Annals of the rheumatic diseases. 11/2010; 69(11):1934-9.

  To identify patients with localised Wegener's granulomatosis (locWG) to assess whether it occurs as a long-term disease stage or phenotype and to characterise its outcome. Patients in a 'localisedTo identify patients with localised Wegener's granulomatosis (locWG) to assess whether it occurs as a long-term disease stage or phenotype and to characterise its outcome. Patients in a 'localised stage' with histological criteria compatible with WG and a follow-up period of ≥1 year were included. They were prospectively followed at the Vasculitis Center Schleswig-Holstein from 1989 to 2009 and the clinical manifestations, antineutrophil cytoplasmic autoantibodies (ANCA) status and damage were evaluated. Immunosuppression was adapted to disease activity and severity in a step-up regimen. Of 1024 patients with suspected WG, 99 were clinically diagnosed with locWG and 50 fulfilled the inclusion criteria (72% women, median age 43 years, 46% ANCA-positive). The median follow-up was 48 months. All achieved a response to treatment, 34% achieved complete remission, 1-4 relapses occurred in 46%, 5 (10%) had generalised disease (median 6 years after onset). ANCA status was not associated with relapse (p=0.98), transition to generalised disease (p=0.51) or refractory manifestations (p=0.60). 47% required cyclophosphamide for localised manifestations, 36% of them for pulmonary masses and 24% for orbital masses. 66% developed organ damage, mostly due to bony destruction or space obturation (28% saddle nose, 24% septal perforation, 10% orbital wall destruction). There were two deaths that were not related to WG. There is evidence that locWG is a long-term disease stage or phenotype (5% of all patients with WG), 46% of whom are ANCA-positive. LocWG is characterised by destructive and/or space-consuming lesions associated with high relapse rates (46%) and local damage.

• Autoantibodies against the bactericidal/permeability-increasing protein from inflammatory bowel disease patients can impair the antibiotic activity of bactericidal/permeability-increasing protein.

  Authors: Susanne Schinke, Klaus Fellermann, Karen Herlyn, Philipp H Reichel, Rilana Fundke, Eduard F Stange, Wolfgang L Gross, Hendrik Schultz

  Inflammatory bowel diseases. 12/2004; 10(6):763-70.

  Bactericidal/permeability-increasing protein (BPI) is an antineutrophil cytoplasmic autoantibody (ANCA) target antigen in inflammatory bowel disease (IBD). The aim of this study was to characterizeBactericidal/permeability-increasing protein (BPI) is an antineutrophil cytoplasmic autoantibody (ANCA) target antigen in inflammatory bowel disease (IBD). The aim of this study was to characterize binding regions of BPI-autoantibodies and to analyze their ability to block the antibiotic effect of BPI. Sera of 24 ulcerative colitis and Crohn's disease patients were examined in indirect immuno-fluorescence, ANCA enzyme-linked immunosorbent assay (ELISA), and by epitope mapping with 13mer peptides and Western blot for presence of BPI-autoantibodies. IgG preparations were used to determine inhibition of BPI's antimicrobial function by BPI-autoantibodies in a bacterial growth inhibition assay. BPI-autoantibodies were detected by ELISA in 18/24 patients. Epitope mapping and western blotting revealed an additional 3 patients with BPI-autoantibodies. IgG preparations of all patients with Crohn's disease and 9 of 12 ulcerative colitis patients could inhibit the antibiotic function of BPI in vitro as compared with healthy control subjects. Inhibiting BPI-autoantibodies correlated with extraintestinal manifestations, peripheral blood leukocyte counts, and anemia. BPI-autoantibodies recognizing the N-terminal portion were associated with greater mucosal damage and intestinal extent of disease. BPI is a frequent target antigen of autoantibodies in ulcerative colitis and Crohn's disease. Inhibition of the antibiotic function mediated by the N-terminal region of BPI by these autoantibodies may contribute to a proinflammatory environment in IBD patients.

• BPI-ANCA of pediatric cystic fibrosis patients can impair BPI-mediated killing of E. coli DH5alpha in vitro.

  Authors: Hendrik Schultz, Susanne Schinke, Katharina Mosler, Karen Herlyn, Antje Schuster, Wolfgang L Gross

  Pediatric pulmonology. 03/2004; 37(2):158-64.

  Gram-negative bacterial lung infections and chronic bacterial colonization are major threats for pediatric cystic fibrosis (CF) patients. Besides impeded mucociliary clearance, other mechanisms thatGram-negative bacterial lung infections and chronic bacterial colonization are major threats for pediatric cystic fibrosis (CF) patients. Besides impeded mucociliary clearance, other mechanisms that contribute to increased susceptibility to infections are presumed. The bactericidal/permeability-increasing protein (BPI), which is delivered by neutrophil granulocytes and mucosal epithelial cells, is one of the most potent innate antibiotics against Gram-negative bacteria and endotoxin. Antineutrophil cytoplasmic autoantibodies against BPI (BPI-ANCA) have been found in up to 90% of CF patients, and titers correlated inversely with lung function parameters. As major pulmonary damage is mediated by Gram-negative bacteria and their products, the question was raised as to whether BPI-ANCA can inhibit the antibiotic function of BPI in these patients. Sera of 23 pediatric CF patients were analyzed for the presence of BPI-ANCA by indirect immunofluorescence, ELISA, epitope mapping, and Western blotting. Patients' IgG were tested in a bacterial growth inhibition assay with recombinant BPI (rBPI) and an amino-terminal fragment of BPI (rBPI(21)) that retains antibiotic activity for inhibition of the antibiotic function of BPI against E. coli DH5alpha in vitro. BPI was recognized by 21 of 23 patients' sera in our detection assays. Thirteen of 23 patients' BPI-ANCA (56%) could inhibit the antibiotic function in vitro. Moreover, epitope mapping over the whole BPI sequence revealed that more patients' BPI-ANCA recognize the amino-terminal part of BPI than can be detected by ELISA. Thus, in pediatric CF patients, BPI-ANCA may contribute to diminished bacterial clearance by inhibiting the antibiotic function of BPI.