Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
1.
Article in English | MEDLINE | ID: mdl-31836640

ABSTRACT

OBJECTIVE: To address the frequency of myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) in an unselected large cohort of adults with MS. METHODS: This is a cross-sectional study in 2 MS expert centers (Lyon and Strasbourg University Hospitals, France) between December 1, 2017, and June 31, 2018. Patients aged ≥18 years with a definite diagnosis of MS according to 2010 McDonald criteria were tested for MOG-Ab by using a cell-based assay (CBA) in Lyon and subsequently included. Positive samples were tested by investigators blinded to the first result with a second assay in a different laboratory (Barcelona, Spain) by using the same plasmid and secondary Ab. RESULTS: Serum samples from 685 consecutive patients with MS were analyzed for MOG-Ab. Median disease duration at sampling was 11.5 (interquartile range, 5.8-17.7) years, and 72% were women. Two (0.3%) patients resulted to be MOG-Ab-positive. The 2 patients were women aged 42 and 38 at disease onset and were diagnosed with secondary and primary progressive forms of MS, respectively. This positive result was confirmed by the CBA in Barcelona. CONCLUSION: Our findings indicate that MOG-Ab are exceptional in MS phenotype, suggesting that the MOG-Ab testing should not be performed in typical MS presentation.


Subject(s)
Autoantibodies/blood , Multiple Sclerosis/blood , Myelin-Oligodendrocyte Glycoprotein/immunology , Adolescent , Adult , Aged , Cross-Sectional Studies , Female , HEK293 Cells , Humans , Male , Middle Aged , Multiple Sclerosis, Chronic Progressive/blood , Young Adult
3.
J Neurol ; 266(4): 806-815, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30607536

ABSTRACT

OBJECTIVE: To analyze whether myelin oligodendrocyte glycoprotein antibody (MOG-Ab) titres at onset of the disease were different according to the clinical phenotype at presentation, and to investigate whether the titres were associated with risk of further relapses or predicted clinical outcome in adult patients. Finally, we assessed an alternative method to the classical measurement of MOG-Ab levels by serial dilutions. METHODS: This is a retrospective study including 79 MOG-Ab-positive adult patients, whose samples were obtained at first episode. MOG-Ab were tested by cell-based assay. HEK293 cells were transfected (tHEK293) with human-MOG plasmid. Non-tHEK293 cells were used as negative controls. Assessment of antibody titres was performed by serial dilution, and delta mean fluorescence intensity ratio signal (MOG-ratio ΔMFI) by flow cytometry. MOG-ratio ΔMFI was calculated as follows: (MFI tHEK293cells- MFI non-tHEK293cells)/MFI non-tHEK293cells. MOG-ratio ΔMFI was calculated from the first serum dilution at 1:320. The association between MOG-Ab titres and risk of relapse was analyzed by Cox regression. The association between MOG-Ab titres and visual or motor disability at last follow-up was performed by binary logistic regression. Poor visual outcome was defined when patients displayed some degree of visual disability (visual acuity [VA] < 20/20) and poor motor outcome when patients displayed some degree of motor disability (Disability Status Scale [DSS] > 1). We also investigated correlations between MOG-Ab titres and MOG-ratio ΔMFI. RESULTS: MOG-Ab titres were higher in Caucasians than in those with other ethnicities, and in patients with a more severe VA (VA ≤ 20/100) or motor disability (DSS ≥ 3.0) at onset (p = 0.006, 0.034, and 0.058, respectively). MOG-Ab titres were not associated with risk of relapses or with the final clinical outcome. MOG-ratio ΔMFI correlated with MOG-Ab titres in the whole cohort (ρ = 0.90; p < 0.001), and when stratified by initial clinical phenotype. CONCLUSION: High MOG-Ab titres at onset are associated with a more severe presentation, but do not predict the future disease course. MOG-ratio ΔMFI is an alternative and straightforward method to determine MOG-Ab levels.


Subject(s)
Autoantibodies/blood , Demyelinating Diseases/immunology , Myelin-Oligodendrocyte Glycoprotein/immunology , Myelitis/immunology , Optic Neuritis/immunology , Adolescent , Adult , Biological Assay , Demyelinating Diseases/blood , Demyelinating Diseases/therapy , Disease Progression , Female , Follow-Up Studies , HEK293 Cells , Humans , Male , Middle Aged , Myelitis/blood , Myelitis/therapy , Optic Neuritis/blood , Optic Neuritis/therapy , Prognosis , Recurrence , Retrospective Studies , Young Adult
4.
J Neurol ; 264(9): 1945-1955, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28770374

ABSTRACT

Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) have been reported in acute demyelinating encephalomyelitis (ADEM), optic neuritis (ON), and neuromyelitis optica spectrum disorders (NMOSD) in adults and pediatrics. We aimed to delineate the common features of MOG-Ab-related disorders in children and adults, and report uncommon presentations. Twenty-seven consecutive pediatric and adult patients testing positive for MOG-Ab, with a minimum follow-up of 6 months, were included. Comprehensive epidemiological, clinical, radiological, and laboratory data were retrospectively analyzed. Additionally, we compared radiological features between ADEM MOG-Ab-positive patients, and a group of ADEM MOG-Ab-negative ones, recruited during the same period. Among the whole cohort, 13 (48.1%) were pediatric, and 14 (51.9%) were female. MOG-Ab-related disorders comprised eight ADEM, eight ON, five isolated myelitis, four with NMOSD and two patients with multiple sclerosis, at last follow-up. After a median follow-up of 17.8 months, 11 (40.7%) patients presented a relapse. The most frequent clinical phenotype at onset was encephalopathy in pediatrics (53.9%) and myelitis in adults (50%) (p = 0.013). There were no other differences between both groups. When comparing ADEM MOG-Ab positive and negative patients, bilateral thalamic lesions were more often found in the positive group (p = 0.010). Unusual presentations were identified in three patients: patchy spinal cord gadolinium-enhancing lesions, an associated teratoma, and one presented with status epilepticus. MOG-Ab-related disorders shared common clinical and prognostic features, but encompass a spectrum wider than recently reported.


Subject(s)
Autoantibodies/blood , Encephalomyelitis , Myelin-Oligodendrocyte Glycoprotein/immunology , Neuromyelitis Optica , Optic Neuritis , Adolescent , Adult , Age Factors , Aged , Child , Child, Preschool , Cohort Studies , Encephalomyelitis/blood , Encephalomyelitis/diagnostic imaging , Encephalomyelitis/immunology , Female , Humans , Infant , Magnetic Resonance Imaging , Male , Middle Aged , Neuromyelitis Optica/blood , Neuromyelitis Optica/diagnostic imaging , Neuromyelitis Optica/immunology , Optic Neuritis/blood , Optic Neuritis/diagnostic imaging , Optic Neuritis/immunology , Statistics, Nonparametric , Young Adult
5.
Nat Genet ; 44(8): 916-21, 2012 Jul 08.
Article in English | MEDLINE | ID: mdl-22772371

ABSTRACT

A predisposition for thoracic aortic aneurysms leading to acute aortic dissections can be inherited in families in an autosomal dominant manner. Genome-wide linkage analysis of two large unrelated families with thoracic aortic disease followed by whole-exome sequencing of affected relatives identified causative mutations in TGFB2. These mutations-a frameshift mutation in exon 6 and a nonsense mutation in exon 4-segregated with disease with a combined logarithm of odds (LOD) score of 7.7. Sanger sequencing of 276 probands from families with inherited thoracic aortic disease identified 2 additional TGFB2 mutations. TGFB2 encodes transforming growth factor (TGF)-ß2, and the mutations are predicted to cause haploinsufficiency for TGFB2; however, aortic tissue from cases paradoxically shows increased TGF-ß2 expression and immunostaining. Thus, haploinsufficiency for TGFB2 predisposes to thoracic aortic disease, suggesting that the initial pathway driving disease is decreased cellular TGF-ß2 levels leading to a secondary increase in TGF-ß2 production in the diseased aorta.


Subject(s)
Aortic Aneurysm, Thoracic/genetics , Aortic Dissection/genetics , Marfan Syndrome/genetics , Mutation , Transforming Growth Factor beta2/genetics , Aortic Dissection/metabolism , Aortic Dissection/pathology , Aortic Aneurysm, Thoracic/metabolism , Aortic Aneurysm, Thoracic/pathology , Codon, Nonsense , Exome , Female , Frameshift Mutation , Genetic Predisposition to Disease , Genome-Wide Association Study , Haploinsufficiency , Humans , Lod Score , Male , Pedigree , Transforming Growth Factor beta2/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...