GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 1 ( 2021-01-05)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 1 ( 2021-01-05)
    Abstract: Multiple sclerosis (MS) disease risk is associated with reduced sun-exposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in the setting of two multicenter cohort studies ( n NationMS = 946, n BIONAT = 990). Additionally, effect-modification by medication and photosensitivity-associated MC1R variants was assessed. High serum vitD was associated with a reduced MS severity score (MSSS), reduced risk for relapses, and lower disability accumulation over time. Low latitude was associated with higher vitD, lower MSSS, fewer gadolinium-enhancing lesions, and lower disability accumulation. The association of latitude with disability was lacking in IFN-β–treated patients. In carriers of MC1R :rs1805008(T), who reported increased sensitivity toward sunlight, lower latitude was associated with higher MRI activity, whereas for noncarriers there was less MRI activity at lower latitudes. In a further exploratory approach, the effect of ultraviolet (UV)-phototherapy on the transcriptome of immune cells of MS patients was assessed using samples from an earlier study. Phototherapy induced a vitD and type I IFN signature that was most apparent in monocytes but that could also be detected in B and T cells. In summary, our study suggests beneficial effects of sun exposure on established MS, as demonstrated by a correlative network between the three factors: Latitude, vitD, and disease severity. However, sun exposure might be detrimental for photosensitive patients. Furthermore, a direct induction of type I IFNs through sun exposure could be another mechanism of UV-mediated immune-modulation in MS.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2018457118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    A genome-wide association study in autoimmune neurological syndromes with anti-GAD65 autoantibodies
    Oxford University Press (OUP) ; 2023
    In:  Brain Vol. 146, No. 3 ( 2023-03-01), p. 977-990
    Details
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 3 ( 2023-03-01), p. 977-990
    Abstract: Autoimmune neurological syndromes (AINS) with autoantibodies against the 65 kDa isoform of the glutamic acid decarboxylase (GAD65) present with limbic encephalitis, including temporal lobe seizures or epilepsy, cerebellitis with ataxia, and stiff-person-syndrome or overlap forms. Anti-GAD65 autoantibodies are also detected in autoimmune diabetes mellitus, which has a strong genetic susceptibility conferred by human leukocyte antigen (HLA) and non-HLA genomic regions. We investigated the genetic predisposition in patients with anti-GAD65 AINS. We performed a genome-wide association study (GWAS) and an association analysis of the HLA region in a large German cohort of 1214 individuals. These included 167 patients with anti-GAD65 AINS, recruited by the German Network for Research on Autoimmune Encephalitis (GENERATE), and 1047 individuals without neurological or endocrine disease as population-based controls. Predictions of protein expression changes based on GWAS findings were further explored and validated in the CSF proteome of a virtually independent cohort of 10 patients with GAD65-AINS and 10 controls. Our GWAS identified 16 genome-wide significant (P & lt; 5 × 10−8) loci for the susceptibility to anti-GAD65 AINS. The top variant, rs2535288 [P = 4.42 × 10−16, odds ratio (OR) = 0.26, 95% confidence interval (CI) = 0.187–0.358], localized to an intergenic segment in the middle of the HLA class I region. The great majority of variants in these loci ( & gt;90%) mapped to non-coding regions of the genome. Over 40% of the variants have known regulatory functions on the expression of 48 genes in disease relevant cells and tissues, mainly CD4+ T cells and the cerebral cortex. The annotation of epigenomic marks suggested specificity for neural and immune cells. A network analysis of the implicated protein-coding genes highlighted the role of protein kinase C beta (PRKCB) and identified an enrichment of numerous biological pathways participating in immunity and neural function. Analysis of the classical HLA alleles and haplotypes showed no genome-wide significant associations. The strongest associations were found for the DQA1*03:01-DQB1*03:02-DRB1*04:01HLA haplotype (P = 4.39 × 10−4, OR = 2.5, 95%CI = 1.499–4.157) and DRB1*04:01 allele (P = 8.3 × 10−5, OR = 2.4, 95%CI = 1.548–3.682) identified in our cohort. As predicted, the CSF proteome showed differential levels of five proteins (HLA-A/B, C4A, ATG4D and NEO1) of expression quantitative trait loci genes from our GWAS in the CSF proteome of anti-GAD65 AINS. These findings suggest a strong genetic predisposition with direct functional implications for immunity and neural function in anti-GAD65 AINS, mainly conferred by genomic regions outside the classical HLA alleles.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac119
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474117-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Contribution of spinal cord biopsy to diagnosis of aquaporin-4 antibody positive neuromyelitis optica spectrum disorder
    SAGE Publications ; 2014
    In:  Multiple Sclerosis Journal Vol. 20, No. 7 ( 2014-06), p. 882-888
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 20, No. 7 ( 2014-06), p. 882-888
    Abstract: Longitudinally extensive transverse myelitis is characteristic but not pathognomonic for neuromyelitis optica spectrum disorders (NMOSDs) and may mimic local tumors. In this retrospective study based on a cohort of 175 NMOSD patients we identified seven patients who initially presented with a longitudinally extensive spinal cord lesion and underwent spinal cord biopsy due to magnetic resonance imaging (MRI)-suspected malignancies. Remarkably, routine neuropathology was inconclusive and did not guide the diagnostic process to anti-aquaporin-4 (AQP4)-seropositive NMOSD. Serious postoperative complications occurred in 5/7 patients and persisted during follow-up in 2/7 patients (29%). Considering these sequelae, AQP4-antibody testing should be mandatory in patients with inconclusive longitudinally extensive spinal cord lesions prior to biopsy.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458513510981
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
    detail.hit.zdb_id: 2008225-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Influence of female sex and fertile age on neuromyelitis optica spectrum disorders
    SAGE Publications ; 2017
    In:  Multiple Sclerosis Journal Vol. 23, No. 8 ( 2017-07), p. 1092-1103
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 23, No. 8 ( 2017-07), p. 1092-1103
    Abstract: Gender and age at onset are important epidemiological factors influencing prevalence, clinical presentation, and treatment response in autoimmune diseases. Objective: To evaluate the impact of female sex and fertile age on aquaporin-4-antibody (AQP4-ab) status, attack localization, and response to attack treatment in patients with neuromyelitis optica (NMO) and its spectrum disorders (neuromyelitis optica spectrum disorder (NMOSD)). Methods: Female-to-male ratios, diagnosis at last visit (NMO vs NMOSD), attack localization, attack treatment, and outcome were compared according to sex and age at disease or attack onset. Results: A total of 186 NMO/SD patients (82% female) were included. In AQP4-ab-positive patients, female predominance was most pronounced during fertile age (female-to-male ratio 23:1). Female patients were more likely to be positive for AQP4-abs (92% vs 55%; p  〈  0.001). Interval between onset and diagnosis of NMO/SD was longer in women than in men (mean 54 vs 27 months; p = 0.023). In women, attacks occurring ⩽40 years of age were more likely to show complete remission ( p = 0.003) and better response to high-dose intravenous steroids ( p = 0.005) compared to woman at 〉 40 years. Conclusion: Our data suggest an influence of sex and age on susceptibility to AQP4-ab-positive NMO/SD. Genetic and hormonal factors might contribute to pathophysiology of NMO/SD.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458516671203
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2008225-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    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
    Springer Science and Business Media LLC ; 2016
    In:  Journal of Neurology Vol. 263, No. 12 ( 2016-12), p. 2499-2504
    Details
    In: Journal of Neurology, Springer Science and Business Media LLC, Vol. 263, No. 12 ( 2016-12), p. 2499-2504
    Type of Medium: Online Resource
    ISSN: 0340-5354 , 1432-1459
    URL: Article
    DOI: 10.1007/s00415-016-8302-1
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 1421299-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Apheresis therapies for NMOSD attacks : A retrospective study of 207 therapeutic interventions
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Neurology - Neuroimmunology Neuroinflammation Vol. 5, No. 6 ( 2018-11), p. e504-
    Details
    In: Neurology - Neuroimmunology Neuroinflammation, Ovid Technologies (Wolters Kluwer Health), Vol. 5, No. 6 ( 2018-11), p. e504-
    Abstract: To analyze whether 1 of the 2 apheresis techniques, therapeutic plasma exchange (PE) or immunoadsorption (IA), is superior in treating neuromyelitis optica spectrum disorder (NMOSD) attacks and to identify predictive factors for complete remission (CR). Methods This retrospective cohort study was based on the registry of the German Neuromyelitis Optica Study Group, a nationwide network established in 2008. It recruited patients with neuromyelitis optica diagnosed according to the 2006 Wingerchuk criteria or with aquaporin-4 (AQP4-ab)-antibody–seropositive NMOSD treated at 6 regional hospitals and 16 tertiary referral centers until March 2013. Besides descriptive data analysis of patient and attack characteristics, generalized estimation equation (GEE) analyses were applied to compare the effectiveness of the 2 apheresis techniques. A GEE model was generated to assess predictors of outcome. Results Two hundred and seven attacks in 105 patients (87% AQP4-ab-antibody seropositive) were treated with at least 1 apheresis therapy. Neither PE nor IA was proven superior in the therapy of NMOSD attacks. CR was only achieved with early apheresis therapy. Strong predictors for CR were the use of apheresis therapy as first-line therapy (OR 12.27, 95% CI: 1.04–144.91, p = 0.047), time from onset of attack to start of therapy in days (OR 0.94, 95% CI: 0.89–0.99, p = 0.014), the presence of AQP4-ab-antibodies (OR 33.34, 95% CI: 1.76–631.17, p = 0.019), and monofocal attack manifestation (OR 4.71, 95% CI: 1.03–21.62, p = 0.046). Conclusions Our findings suggest early use of an apheresis therapy in NMOSD attacks, particularly in AQP4-ab-seropositive patients. No superiority was shown for one of the 2 apheresis techniques. Classification of evidence This study provides Class IV evidence that for patients with NMOSD, neither PE nor IA is superior in the treatment of attacks.
    Type of Medium: Online Resource
    ISSN: 2332-7812
    URL: Article
    DOI: 10.1212/NXI.0000000000000504
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2767740-0
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses
    Wiley ; 2016
    In:  Annals of Neurology Vol. 79, No. 2 ( 2016-02), p. 206-216
    Details
    In: Annals of Neurology, Wiley, Vol. 79, No. 2 ( 2016-02), p. 206-216
    Abstract: Neuromyelitis optica (NMO) attacks often are severe, are difficult to treat, and leave residual deficits. Here, we analyzed the frequency, sequence, and efficacy of therapies used for NMO attacks. Methods A retrospective review was made of patient records to assess demographic/diagnostic data, attack characteristics, therapies, and the short‐term remission status (complete remission [CR], partial remission [PR] , no remission [NR]). Inclusion criteria were NMO according to Wingerchuk's 2006 criteria or aquaporin‐4 antibody–positive NMO spectrum disorder (NMOSD). Remission status was analyzed with generalized estimating equations (GEEs), a patient‐based statistical approach. Results A total of 871 attacks in 185 patients (142 NMO/43 NMOSD, 82% female) were analyzed. The 1,153 treatment courses comprised high‐dose intravenous steroids (HD‐S; n = 810), plasma exchange (PE; n = 192), immunoadsorption (IA; n = 38), other (n = 80), and unknown (n = 33) therapies. The first treatment course led to CR in 19.1%, PR in 64.5%, and NR in 16.4% of attacks. Second, third, fourth, and fifth treatment courses were given in 28.2%, 7.1%, 1.4%, and 0.5% of attacks, respectively. This escalation of attack therapy significantly improved outcome ( p   〈  0.001, Bowker test). Remission rates were higher for isolated optic neuritis versus isolated myelitis ( p   〈  0.001), and for unilateral versus bilateral optic neuritis ( p  = 0.020). Isolated myelitis responded better to PE/IA than to HD‐S as first treatment course ( p  = 0.037). Predictors of CR in multivariate GEE analysis were age (odds ratio [OR] = 0.97, p  = 0.011), presence of myelitis (OR = 0.38, p  = 0.002), CR from previous attack (OR = 6.85, p   〈  0.001), and first‐line PE/IA versus HD‐S (OR = 4.38, p  = 0.006). Interpretation Particularly myelitis and bilateral optic neuritis have poor remission rates. Escalation of attack therapy improves outcome. PE/IA may increase recovery in isolated myelitis. Ann Neurol 2016;79:206–216
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v79.2
    DOI: 10.1002/ana.24554
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2037912-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease
    Oxford University Press (OUP) ; 2023
    In:  Brain Vol. 146, No. 2 ( 2023-02-13), p. 600-611
    Details
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 2 ( 2023-02-13), p. 600-611
    Abstract: Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported. Data on immunotherapy are limited, and its efficacy remains controversial. In this study, we retrospectively investigated an anti-IgLON5 disease cohort with special focus on clinical, serological and genetic predictors of the immunotherapy response and long-term outcome. Patients were recruited from the GENERATE (German Network for Research on Autoimmune Encephalitis) registry. Along with clinical parameters, anti-IgLON5 immunoglobulin (Ig)G in serum and CSF, anti-IgLON5 IgG1-4, IgA and IgM in serum, neurofilament light chain and glial fibrillary acidic protein in serum as well as human leukocyte antigen-genotypes were determined. We identified 53 patients (symptom onset 63.8 ± 10.3 years, female:male 1:1.5). The most frequent initial clinical presentations were bulbar syndrome, hyperkinetic syndrome or isolated sleep disorder [at least one symptom present in 38% (20/53)]. At the time of diagnosis, the majority of patients had a generalized multi-systemic phenotype; nevertheless, 21% (11/53) still had an isolated brainstem syndrome and/ or a characteristic sleep disorder only. About one third of patients [28% (15/53)] reported subacute disease onset and 51% (27/53) relapse-like exacerbations during the disease course. Inflammatory CSF changes were evident in 37% (19/51) and increased blood-CSF-barrier permeability in 46% (21/46). CSF cell count significantly decreased, while serum anti-IgLON5 IgG titre increased with disease duration. The presence of human leukocyte antigen-DRB1*10:01 [55% (24/44)] was associated with higher serum anti-IgLON5 IgG titres. Neurofilament light chain and glial fibrillary acidic protein in serum were substantially increased (71.1 ± 103.9 pg/ml and 126.7 ± 73.3 pg/ml, respectively). First-line immunotherapy of relapse-like acute-to-subacute exacerbation episodes resulted in improvement in 41% (11/27) of patients and early initiation within the first 6 weeks was a predictor for therapy response. Sixty-eight per cent (36/53) of patients were treated with long-term immunotherapy and 75% (27/36) of these experienced no further disease progression (observation period of 20.2 ± 15.4 months). Long-term immunotherapy initiation during the first year after onset and low pre-treatment neurofilament light chain were significant predictors for a better outcome. In conclusion, subacute disease onset and early inflammatory CSF changes support the primary role of autoimmune mechanisms at least at initial stages of anti-IgLON5 disease. Early immunotherapy, prior to advanced neurodegeneration, is associated with a better long-term clinical outcome. Low serum neurofilament light chain at treatment initiation may serve as a potential biomarker of the immunotherapy response.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac090
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474117-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients
    Springer Science and Business Media LLC ; 2012
    In:  Journal of Neuroinflammation Vol. 9, No. 1 ( 2012-12)
    Details
    In: Journal of Neuroinflammation, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2012-12)
    Abstract: 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. Conclusion This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.
    Type of Medium: Online Resource
    ISSN: 1742-2094
    URL: Article
    DOI: 10.1186/1742-2094-9-14
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2012
    detail.hit.zdb_id: 2156455-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response
    BMJ ; 2017
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 88, No. 8 ( 2017-08), p. 639-647
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 88, No. 8 ( 2017-08), p. 639-647
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    DOI: 10.1136/jnnp-2017-315603
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2017
    detail.hit.zdb_id: 1480429-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...