@article{BoivinBeyersdorfPalmetal.2015,
  author    = {Boivin, Val{\´e}rie and Beyersdorf, Niklas and Palm, Dieter and Nikolaev, Viacheslav O. and Schlipp, Angela and M{\"u}ller, Justus and Schmidt, Doris and Kocoski, Vladimir and Kerkau, Thomas and H{\"u}nig, Thomas and Ertl, Georg and Lohse, Martin J. and Jahns, Roland},
  title     = {Novel Receptor-Derived Cyclopeptides to Treat Heart Failure Caused by \(Anti-β_1-Adrenoceptor\) Antibodies in a Human-Analogous Rat Model},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {2},
  doi       = {10.1371/journal.pone.0117589},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126028},
  pages     = {e0117589},
  year      = {2015},
  abstract  = {Despite recent therapeutic advances the prognosis of heart failure remains poor. Recent research suggests that heart failure is a heterogeneous syndrome and that many patients have stimulating auto-antibodies directed against the second extracellular loop of the \(β_1\) adrenergic receptor \((β_1EC2)\). In a human-analogous rat model such antibodies cause myocyte damage and heart failure. Here we used this model to test a novel antibody-directed strategy aiming to prevent and/or treat antibody-induced cardiomyopathy. To generate heart failure, we immunised n = 76/114 rats with a fusion protein containing the human β1EC2 (amino-acids 195-225) every 4 weeks; n = 38/114 rats were control-injected with 0.9\% NaCl. Intravenous application of a novel cyclic peptide mimicking \(β_1EC2\) (\(β_1EC2-CP\), 1.0 mg/kg every 4 weeks) or administration of the \(β_1-blocker\) bisoprolol (15 mg/kg/day orally) was initiated either 6 weeks (cardiac function still normal, prevention-study, n = 24 (16 treated vs. 8 untreated)) or 8.5 months after the 1st immunisation (onset of cardiomyopathy, therapy-study, n = 52 (40 treated vs. 12 untreated)); n = 8/52 rats from the therapy-study received \(β_1EC2-CP/bisoprolol\) co-treatment. We found that \(β_1EC2-CP\) prevented and (alone or as add-on drug) treated antibody-induced cardiac damage in the rat, and that its efficacy was superior to mono-treatment with bisoprolol, a standard drug in heart failure. While bisoprolol mono-therapy was able to stop disease-progression, \(β_1EC2-CP\) mono-therapy -or as an add-on to bisoprolol- almost fully reversed antibody-induced cardiac damage. The cyclo¬peptide acted both by scavenging free \(anti-β_1EC2-antibodies\) and by targeting \(β_1EC2\)-specific memory B-cells involved in antibody-production. Our model provides the basis for the clinical translation of a novel double-acting therapeutic strategy that scavenges harmful \(anti-β_1EC2-antibodies\) and also selectively depletes memory B-cells involved in the production of such antibodies. Treatment with immuno-modulating cyclopeptides alone or as an add-on to \(β_1\)-blockade represents a promising new therapeutic option in immune-mediated heart failure.},
  language  = {en}
}
@article{KneitzKerkauMuelleretal.1993,
  author    = {Kneitz, Christian and Kerkau, Thomas and M{\"u}ller, Justus and Coulibaly, Cheick and Stahl-Henning, Christiane and Hunsmann, Gerhard and H{\"u}nig, Thomas and Schimpl, Anneliese},
  title     = {Early phenotypic and functional alterations in lymphocytes from simian immunodeficiency virus infected macaques},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32593},
  year      = {1993},
  abstract  = {Phenotypic and functional changes in lymphocytes from rhesus monkeys (Macaca mulatta) were investigated during the first 6 months after infection with SIVmac 32H. Animals preimmunized with keyhole limpet hemocyanin (KLH) were sacrificed l, 3, 6, 12, and 24 weeks post infection. Subset composition and function of lymphocytes from blood, spleen, lymph node and thymus were analysed. In addition to a rapid decline in CD4/CD8 ratios, a massive reduction in CD29+CD4+ cells was seen in the periphery. Although depletion of this subset was observed throughout the course of this experiment, the loss of proliferative T cell responses was most pronounced very early after infection and partially recovered after Month 3. Polyclonal cytotoxic responses were only slightly affected. In the thymus, a gradual, but moderate loss of CD4 + CD8 + immature thymocytes, and a relative increase in both CD4 + and CD8 + mature subsets was observed. Infectious virus was readily recovered from homogenates of lymph node and spleen, but not of thymus tissue. Interestingly, however, virus was detected in thymocytes from all infected animals by cocultivation with a simian immunodeficiency virus (SIV) susceptible cell line.},
  language  = {en}
}