Nejvíce citovaný článek - PubMed ID 16087714
Inebilizumab, a humanized, glycoengineered, IgG1 monoclonal antibody that depletes CD19+ B-cells, is approved to treat aquaporin 4 (AQP4) IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab is afucosylated and engineered for enhanced affinity to Fc receptor III-A (FCGR3A) receptors on natural killer cells to maximize antibody-dependent cellular cytotoxicity. Previously, the F allele polymorphism at amino acid 158 of the FCGR3A gene (F158) was shown to decrease IgG-binding affinity and reduce rituximab (anti-CD20) efficacy for NMOSD attack prevention. In contrast, our current findings from inebilizumab-treated NMOSD patients indicate similar clinical outcomes between those with F158 and V158 allele genotypes.
- MeSH
- akvaporin 4 genetika MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- imunoglobulin G MeSH
- lidé MeSH
- neuromyelitis optica * farmakoterapie genetika MeSH
- receptory IgG genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- akvaporin 4 MeSH
- FCGR3A protein, human MeSH Prohlížeč
- humanizované monoklonální protilátky MeSH
- imunoglobulin G MeSH
- inebilizumab MeSH Prohlížeč
- receptory IgG MeSH
Cumulative evidence along several lines indicates that B cells play an important role in the pathological course of multiple sclerosis (MS), neuromyelitisoptica spectrum disorders (NMOSD) and related CNS diseases. This has prompted extensive research in exploring the utility of targeting B cells to contain disease activity in these disorders. In this review, we first recapitulate the development of B cells from their origin in the bone marrow to their migration to the periphery, including the expression of therapy-relevant surface immunoglobulin isotypes. Not only the ability of B cells to produce cytokines and immunoglobulins seems to be essential in driving neuroinflammation, but also their regulatory functions strongly impact pathobiology. We then critically assess studies of B cell depleting therapies, including CD20 and CD19 targeting monoclonal antibodies, as well as the new class of B cell modulating substances, Bruton´s tyrosinekinase (BTK) inhibitors, in MS, NMOSD and MOGAD.
- Klíčová slova
- B cell depletion, autoimmune disease of the central nervous system, multiple sclerosis (MS), myelin oligodendrocyte glycoprotein associated autoimmune disease (MOGAD), neuromyelitisoptica spectrum disorders (NMOSD),
- MeSH
- autoimunitní nemoci * farmakoterapie MeSH
- autoprotilátky MeSH
- B-lymfocyty MeSH
- centrální nervový systém MeSH
- lidé MeSH
- roztroušená skleróza * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- autoprotilátky MeSH
OBJECTIVE: Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD). METHODS: Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1). RESULTS: Results of tests on 92 controls identified 12assays as highly specific (0-1 false-positive results). 32 samples from 50 (64%) NMO sera and 34 from 51 (67%) NMOSD sera were positive on at least two of the 12 highly specific assays, leaving 35 patients with seronegative NMO/spectrum disorder (SD). On the basis of a combination of clinical phenotype and the highly specific assays, 66 AQP4-Ab seropositive samples were used to establish the sensitivities (51.5-100%) of all 21 assays. The specificities (85.8-100%) were based on 92 control samples and 35 seronegative NMO/SD patient samples. CONCLUSIONS: The cell-based assays were most sensitive and specific overall, but immunohistochemistry or flow cytometry could be equally accurate in specialist centres. Since patients with AQP4-Ab negative NMO/SD require different management, the use of both appropriate control samples and defined seronegative NMOSD samples is essential to evaluate these assays in a clinically meaningful way. The process described here can be applied to the evaluation of other antibody assays in the newly evolving field of autoimmune neurology.
- MeSH
- akvaporin 4 krev imunologie MeSH
- autoprotilátky krev imunologie MeSH
- ELISA metody MeSH
- imunohistochemie metody MeSH
- lidé MeSH
- neuromyelitis optica krev imunologie MeSH
- senzitivita a specificita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- akvaporin 4 MeSH
- autoprotilátky MeSH
OBJECTIVE: To quantify the periventricular venous density in neuromyelitis optica spectrum disease (NMOSD) in comparison to that in patients with multiple sclerosis (MS) and healthy control subjects. MATERIALS AND METHODS: Sixteen patients with NMOSD, 16 patients with MS and 16 healthy control subjects underwent 7.0-Tesla (7T) MRI. The imaging protocol included T2*-weighted (T2*w) fast low angle-shot (FLASH) and fluid-attenuated inversion recovery (FLAIR) sequences. The periventricular venous area (PVA) was manually determined by a blinded investigator in order to estimate the periventricular venous density in a region of interest-based approach. RESULTS: No significant differences in periventricular venous density indicated by PVA were detectable in NMOSD versus healthy controls (p = 0.226). In contrast, PVA was significantly reduced in MS patients compared to healthy controls (p = 0.013). CONCLUSION: Unlike patients with MS, those suffering from NMOSD did not show reduced venous visibility. This finding may underscore primary and secondary pathophysiological differences between these two distinct diseases of the central nervous system.
- Klíčová slova
- 7T MRI, Multiple sclerosis, Neuromyelitis optica, Ultrahigh-field MRI, Venous density,
- MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mladý dospělý MeSH
- mozek diagnostické zobrazování patologie MeSH
- neuromyelitis optica diagnostické zobrazování patologie MeSH
- roztroušená skleróza diagnostické zobrazování patologie MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- vény diagnostické zobrazování patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The immune system generates antibodies and antigen-specific T-cells as basic elements of the immune networks that differentiate self from non-self in a finely tuned manner. The antigen-specific nature of immune responses ensures that normal immune activation contains non-self when tolerating self. Here we review the B-1 subset of lymphocytes which produce self-reactive antibodies. By analyzing the IgM class of natural antibodies that recognize antigens from the nervous system, we emphasize that natural antibodies are biomarkers of how the immune system monitors the host. The immune response activated against self can be detrimental when triggered in an autoimmune genetic background. In contrast, tuning immune activity with natural antibodies is a potential therapeutic strategy.
- Klíčová slova
- B-1 cell, CNS inflammation, T-cell activation, autoimmunity, natural auto-antibody,
- Publikační typ
- časopisecké články MeSH
Conventional magnetic resonance imaging (MRI) at 1.5 Tesla (T) is limited by modest spatial resolution and signal-to-noise ratio (SNR), impeding the identification and classification of inflammatory central nervous system changes in current clinical practice. Gaining from enhanced susceptibility effects and improved SNR, ultrahigh field MRI at 7 T depicts inflammatory brain lesions in great detail. This review summarises recent reports on 7 T MRI in neuroinflammatory diseases and addresses the question as to whether ultrahigh field MRI may eventually improve clinical decision-making and personalised disease management.
