TY  - JOUR
A1  - Gómez-Fernández, Paloma
A1  - Lopez de Lapuente Portilla, Aitzkoa
A1  - Astobiza, Ianire
A1  - Mena, Jorge
A1  - Urtasun, Andoni
A1  - Altmann, Vivian
A1  - Matesanz, Fuencisla
A1  - Otaegui, David
A1  - Urcelay, Elena
A1  - Antigüedad, Alfredo
A1  - Malhotra, Sunny
A1  - Montalban, Xavier
A1  - Castillo-Triviño, Tamara
A1  - Espino-Paisán, Laura
A1  - Aktas, Orhan
A1  - Buttmann, Mathias
A1  - Chan, Andrew
A1  - Fontaine, Bertrand
A1  - Gourraud, Pierre-Antoine
A1  - Hecker, Michael
A1  - Hoffjan, Sabine
A1  - Kubisch, Christian
A1  - Kümpfel, Tania
A1  - Luessi, Felix
A1  - Zettl, Uwe K.
A1  - Zipp, Frauke
A1  - Alloza, Iraide
A1  - Comabella, Manuel
A1  - Lill, Christina M.
A1  - Vandenbroeck, Koen
T1  - The rare IL22RA2 signal peptide coding variant rs28385692 decreases secretion of IL-22BP isoform-1, -2 and -3 and is associated with risk for multiple sclerosis
JF  - Cells
N2  - The IL22RA2 locus is associated with risk for multiple sclerosis (MS) but causative variants are yet to be determined. In a single nucleotide polymorphism (SNP) screen of this locus in a Basque population, rs28385692, a rare coding variant substituting Leu for Pro at position 16 emerged significantly (p = 0.02). This variant is located in the signal peptide (SP) shared by the three secreted protein isoforms produced by IL22RA2 (IL-22 binding protein-1(IL-22BPi1), IL-22BPi2 and IL-22BPi3). Genotyping was extended to a Europe-wide case-control dataset and yielded high significance in the full dataset (p = 3.17 × 10\(^{-4}\)). Importantly, logistic regression analyses conditioning on the main known MS-associated SNP at this locus, rs17066096, revealed that this association was independent from the primary association signal in the full case-control dataset. In silico analysis predicted both disruption of the alpha helix of the H-region of the SP and decreased hydrophobicity of this region, ultimately affecting the SP cleavage site. We tested the effect of the p.Leu16Pro variant on the secretion of IL-22BPi1, IL-22BPi2 and IL-22BPi3 and observed that the Pro16 risk allele significantly lowers secretion levels of each of the isoforms to around 50%–60% in comparison to the Leu16 reference allele. Thus, our study suggests that genetically coded decreased levels of IL-22BP isoforms are associated with augmented risk for MS.
KW  - IL22RA2
KW  - IL-22 binding protein isoform
KW  - mutation
KW  - signal peptide
KW  - multiple sclerosis
KW  - autoimmune
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200769
SN  - 2073-4409
VL  - 9
IS  - 1
ER  - 
TY  - THES
A1  - Buchwald, Sina
T1  - Autoimmune Enzephalitiden am Universitätsklinikum Würzburg von 2006-2016
T1  - Cases of autoimmune encephalitis at the Universitätsklinikum Würzburg from 2006-2016
N2  - In den Jahren von 2006 bis 2016 sind am Universitätsklinikum Würzburg insgesamt 26 Patienten mit der Diagnose einer Autoimmunen Enzephalitis behandelt worden. Diese Arbeit zeigt ihre Krankheitsverläufe, Outcome, die gefundenen Antikörper und die Therapien der jeweiligen Patienten. Im zweiten Schritt wurden die Daten mit den in der Literatur bereits beschrieben Fällen verglichen, um Gemeinsamkeiten, aber auch Unterschiede aufzeigen zu können.
N2  - In the time from 2006 to 2016, 26 patients with the diagnosis "autoimmune encephalitis” were treated at the Universitätsklinikum in Würzburg. This paper shows their data, antibody findings, treatments and outcomes. In a second step, this data was compared with cases that have already been described in literature to show similarities and differences.
KW  - Enzephalitis
KW  - Autoimmun
KW  - Encephalitis
KW  - autoimmune
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207202
ER  -