TY  - JOUR
A1  - Huss, André M.
A1  - Halbgebauer, Steffen
A1  - Öckl, Patrick
A1  - Trebst, Corinna
A1  - Spreer, Annette
A1  - Borisow, Nadja
A1  - Harrer, Andrea
A1  - Brecht, Isabel
A1  - Balint, Bettina
A1  - Stich, Oliver
A1  - Schlegel, Sabine
A1  - Retzlaff, Nele
A1  - Winkelmann, Alexander
A1  - Roesler, Romy
A1  - Lauda, Florian
A1  - Yildiz, Özlem
A1  - Voß, Elke
A1  - Muche, Rainer
A1  - Rauer, Sebastian
A1  - Bergh, Florian Then
A1  - Otto, Markus
A1  - Paul, Friedemann
A1  - Wildemann, Brigitte
A1  - Kraus, Jörg
A1  - Ruprecht, Klemens
A1  - Stangel, Martin
A1  - Buttmann, Mathias
A1  - Zettl, Uwe K.
A1  - Tumani, Hayrettin
T1  - Importance of cerebrospinal fluid analysis in the era of McDonald 2010 criteria: a German-Austrian retrospective multicenter study in patients with a clinically isolated syndrome
JF  - Journal of Neurology
N2  - The majority of patients presenting with a first clinical symptom suggestive of multiple sclerosis (MS) do not fulfill the MRI criteria for dissemination in space and time according to the 2010 revision of the McDonald diagnostic criteria for MS and are thus classified as clinically isolated syndrome (CIS). To re-evaluate the utility of cerebrospinal fluid (CSF) analysis in the context of the revised McDonald criteria from 2010, we conducted a retrospective multicenter study aimed at determining the prevalence and predictive value of oligoclonal IgG bands (OCBs) in patients with CIS. Patients were recruited from ten specialized MS centers in Germany and Austria. We collected data from 406 patients; at disease onset, 44/406 (11 %) fulfilled the McDonald 2010 criteria for MS. Intrathecal IgG OCBs were detected in 310/362 (86 %) of CIS patients. Those patients were twice as likely to convert to MS according to McDonald 2010 criteria as OCB-negative individuals (hazard ratio = 2.1, p = 0.0014) and in a shorter time period of 25 months (95 % CI 21-34) compared to 47 months in OCB-negative individuals (95 % CI 36-85). In patients without brain lesions at first attack and presence of intrathecal OCBs (30/44), conversion rate to MS was 60 % (18/30), whereas it was only 21 % (3/14) in those without OCBs. Our data confirm that in patients with CIS the risk of conversion to MS substantially increases if OCBs are present at onset. CSF analysis definitely helps to evaluate the prognosis in patients who do not have MS according to the revised McDonald criteria.
KW  - multiple sklerosis
KW  - MRI criteria
KW  - conversion
KW  - MS
KW  - CSF
KW  - biomarker
KW  - OCB
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186619
VL  - 263
IS  - 12
ER  - 
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  -