@article{IpKronerGrohetal.2012,
  author    = {Ip, Chi Wang and Kroner, Antje and Groh, Janos and Huber, Marianne and Klein, Dennis and Spahn, Irene and Diem, Ricarda and Williams, Sarah K. and Nave, Klaus-Armin and Edgar, Julia M. and Martini, Rudolf},
  title     = {Neuroinflammation by Cytotoxic T-Lymphocytes Impairs Retrograde Axonal Transport in an Oligodendrocyte Mutant Mouse},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {8},
  doi       = {10.1371/journal.pone.0042554},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134982},
  pages     = {e42554},
  year      = {2012},
  abstract  = {Mice overexpressing proteolipid protein (PLP) develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonal transport. PLP overexpression in the absence of T-lymphocytes rescued retrograde axonal transport defects and abolished axonal swellings. Bone marrow transfer from wildtype mice, but not from perforin- or granzyme B-deficient mutants, into lymphocyte-deficient PLP mutant mice led again to impaired axonal transport and the formation of axonal swellings, which are predominantly located at the juxtaparanodal region. This demonstrates that the adaptive immune system, including cytotoxic T-lymphocytes which release perforin and granzyme B, are necessary to perturb axonal integrity in the PLP-transgenic disease model. Based on our observations, so far not attended molecular and cellular players belonging to the immune system should be considered to understand pathogenesis in inherited myelin disorders with progressive axonal damage.},
  language  = {en}
}
@article{JariusRuprechtWildemannetal.2012,
  author    = {Jarius, Sven and Ruprecht, Klemens and Wildemann, Brigitte and Kuempfel, Tania and Ringelstein, Marius and Geis, Christian and Kleiter, Ingo and Kleinschnitz, Christoph and Berthele, Achim and Brettschneider, Johannes and Hellwig, Kerstin and Hemmer, Bernhard and Linker, Ralf A. and Lauda, Florian and Hayrettin, Christoph A. and Tumani, Hayrettin and Melms, Arthur and Trebst, Corinna and Stangel, Martin and Marziniak, Martin and Hoffmann, Frank and Schippling, Sven and Faiss, J{\"u}rgen H. and Neuhaus, Oliver and Ettrich, Barbara and Zentner, Christian and Guthke, Kersten and Hofstadt-van Oy, Ulrich and Reuss, Reinhard and Pellkofer, Hannah and Ziemann, Ulf and Kern, Peter and Wandinger, Klaus P. and Bergh, Florian Then and Boettcher, Tobias and Langel, Stefan and Liebetrau, Martin and Rommer, Paulus S. and Niehaus, Sabine and M{\"u}nch, Christoph and Winkelmann, Alexander and Zettl, Uwe K and Metz, Imke and Veauthier, Christian and Sieb, J{\"o}rn P. and Wilke, Christian and Hartung, Hans P. and Aktas, Orhan and Paul, Friedemann},
  title     = {Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients},
  series = {Journal of Neuroinflammation},
  volume    = {9},
  journal   = {Journal of Neuroinflammation},
  number    = {14},
  doi       = {10.1186/1742-2094-9-14},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133636},
  year      = {2012},
  abstract  = {Background: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. Objective: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. Methods: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3\%). Results: Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of <= 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades <= 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions >= 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.},
  language  = {en}
}
@article{KirylukYifuSannaCherchietal.2012,
  author    = {Kiryluk, Krzysztof and Yifu, Li and Sanna-Cherchi, Simone and Rohanizadegan, Mersedeh and Suzuki, Hitoshi and Eitner, Frank and Snyder, Holly J. and Choi, Murim and Hou, Ping and Scolari, Francesco and Izzi, Claudia and Gigante, Maddalena and Gesualdo, Loreto and Savoldi, Silvana and Amoroso, Antonio and Cusi, Daniele and Zamboli, Pasquale and Julian, Bruce A. and Novak, Jan and Wyatt, Robert J. and Mucha, Krzysztof and Perola, Markus and Kristiansson, Kati and Viktorin, Alexander and Magnusson, Patrik K. and Thorleifsson, Gudmar and Thorsteinsdottir, Unnur and Stefansson, Kari and Boland, Anne and Metzger, Marie and Thibaudin, Lise and Wanner, Christoph and Jager, Kitty J. and Goto, Shin and Maixnerova, Dita and Karnib, Hussein H. and Nagy, Judit and Panzer, Ulf and Xie, Jingyuan and Chen, Nan and Tesar, Vladimir and Narita, Ichiei and Berthoux, Francois and Floege, J{\"u}rgen and Stengel, Benedicte and Zhang, Hong and Lifton, Richard P. and Gharavi, Ali G.},
  title     = {Geographic Differences in Genetic Susceptibility to IgA Nephropathy: GWAS Replication Study and Geospatial Risk Analysis},
  series = {PLoS Genetics},
  volume    = {8},
  journal   = {PLoS Genetics},
  number    = {6},
  doi       = {10.1371/journal.pgen.1002765},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130195},
  pages     = {e1002765},
  year      = {2012},
  abstract  = {IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789), followed by meta-analysis with risk-score modeling in 12 cohorts (N = 10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5x10\(^{-32}\) 3x10\(^{-10}\), with heterogeneity detected only at the PSMB9/TAP1 locus (I\(^{-2}\) = 0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5x10\(^{-4}\)). A seven-SNP genetic risk score, which explained 4.7\% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3x10\(^{-128}\)). This model paralleled the known East-West gradient in disease risk. Moreover, the prediction of a South-North axis was confirmed by registry data showing that the prevalence of IgAN-attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN.},
  language  = {en}
}