Improving the sensitivity of myelin oligodendrocyte glycoprotein-antibody testing: exclusive or predominant MOG-IgG3 seropositivity-a potential diagnostic pitfall in patients with MOG-EM/MOGAD.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD) is the most important differential diagnosis of both multiple sclerosis and neuromyelitis optica spectrum disorders. A recent proposal for new diagnostic criteria for MOG-EM/MOGAD explicitly recommends the use of immunoglobulin G subclass 1 (IgG1)- or IgG crystallizable fragment (Fc) region-specific assays and allows the use of heavy-and-light-chain-(H+L) specific assays for detecting MOG-IgG. By contrast, the utility of MOG-IgG3-specific testing has not been systematically evaluated. OBJECTIVE: To assess whether the use of MOG-IgG3-specific testing can improve the sensitivity of MOG-IgG testing. METHODS: Re-testing of 22 patients with a definite diagnosis of MOG-EM/MOGAD and clearly positive MOG-IgG status initially but negative or equivocal results in H+L- or Fc-specific routine assays later in the disease course (i.e. patients with spontaneous or treatment-driven seroreversion). RESULTS: In accordance with previous studies that had used MOG-IgG1-specific assays, IgG subclass-specific testing yielded a higher sensitivity than testing by non-subclass-specific assays. Using subclass-specific secondary antibodies, 26/27 supposedly seroreverted samples were still clearly positive for MOG-IgG, with MOG-IgG1 being the most frequently detected subclass (25/27 [93%] samples). However, also MOG-IgG3 was detected in 14/27 (52%) samples (from 12/22 [55%] patients). Most strikingly, MOG-IgG3 was the predominant subclass in 8/27 (30%) samples (from 7/22 [32%] patients), with no unequivocal MOG-IgG1 signal in 2 and only a very weak concomitant MOG-IgG1 signal in the other six samples. By contrast, no significant MOG-IgG3 reactivity was seen in 60 control samples (from 42 healthy individuals and 18 patients with MS). Of note, MOG-IgG3 was also detected in the only patient in our cohort previously diagnosed with MOG-IgA+/IgG- MOG-EM/MOGAD, a recently described new disease subvariant. MOG-IgA and MOG-IgM were negative in all other patients tested. CONCLUSIONS: In some patients with MOG-EM/MOGAD, MOG-IgG is either exclusively or predominantly MOG-IgG3. Thus, the use of IgG1-specific assays might only partly overcome the current limitations of MOG-IgG testing and-just like H+L- and Fcγ-specific testing-might overlook some genuinely seropositive patients. This would have potentially significant consequences for the management of patients with MOG-EM/MOGAD. Given that IgG3 chiefly detects proteins and is a strong activator of complement and other effector mechanisms, MOG-IgG3 may be involved in the immunopathogenesis of MOG-EM/MOGAD. Studies on the frequency and dynamics as well as the clinical and therapeutic significance of MOG-IgG3 seropositivity are warranted.

Autoantibody status, neuroradiological and clinical findings in children with acute cerebellitis.

BACKGROUND: Acute cerebellitis (AC) in children and adolescents is an inflammatory disease of the cerebellum due to viral or bacterial infections but also autoimmune-mediated processes. OBJECTIVE: To investigate the frequency of autoantibodies in serum and CSF as well as the neuroradiological features in children with AC. MATERIAL AND METHODS: Children presenting with symptoms suggestive of AC defined as acute/subacute onset of cerebellar symptoms and MRI evidence of cerebellar inflammation or additional CSF pleocytosis, positive oligoclonal bands (OCBs), and/or presence of autoantibodies in case of negative cerebellar MRI. Children fulfilling the above-mentioned criteria and a complete data set including clinical presentation, CSF studies, testing for neuronal/cerebellar and MOG antibodies as well as MRI scans performed at disease onset were eligible for this retrospective multicenter study. RESULTS: 36 patients fulfilled the inclusion criteria for AC (f:m = 14:22, median age 5.5 years). Ataxia was the most common cerebellar symptom present in 30/36 (83 %) in addition to dysmetria (15/36) or dysarthria (13/36). A substantial number of children (21/36) also had signs of encephalitis such as somnolence or seizures. In 10/36 (28 %) children the following autoantibodies (abs) were found: MOG-abs (n = 5) in serum, GFAPα-abs (n = 1) in CSF, GlyR-abs (n = 1) in CSF, mGluR1-abs (n = 1) in CSF and serum. In two further children, antibodies were detected only in serum (GlyR-abs, n = 1; GFAPα-abs, n = 1). MRI signal alterations in cerebellum were found in 30/36 children (83 %). Additional supra- and/or infratentorial lesions were present in 12/36 children, including all five children with MOG-abs. Outcome after a median follow-up of 3 months (range: 1 a 75) was favorable with an mRS ≤2 in 24/36 (67 %) after therapy. Antibody (ab)-positive children were significantly more likely to have a better outcome than ab-negative children (p = .022). CONCLUSION: In nearly 30 % of children in our study with AC, a range of abs was found, underscoring that autoantibody testing in serum and CSF should be included in the work-up of a child with suspected AC. The detection of MOG-abs in AC does expand the MOGAD spectrum.

Entanglement Swapping with Photons Generated on Demand by a Quantum Dot.

Photonic entanglement swapping, the procedure of entangling photons without any direct interaction, is a fundamental test of quantum mechanics and an essential resource to the realization of quantum networks. Probabilistic sources of nonclassical light were used for seminal demonstration of entanglement swapping, but applications in quantum technologies demand push-button operation requiring single quantum emitters. This, however, turned out to be an extraordinary challenge due to the stringent prerequisites on the efficiency and purity of the generation of entangled states. Here we show a proof-of-concept demonstration of all-photonic entanglement swapping with pairs of polarization-entangled photons generated on demand by a GaAs quantum dot without spectral and temporal filtering. Moreover, we develop a theoretical model that quantitatively reproduces the experimental data and provides insights on the critical figures of merit for the performance of the swapping operation. Our theoretical analysis also indicates how to improve state-of-the-art entangled-photon sources to meet the requirements needed for implementation of quantum dots in long-distance quantum communication protocols.

Autoimmune and immunogenetic profile of patients with optic neuritis in a population-based cohort.

BACKGROUND: Optic neuritis (ON) is an inflammatory optic neuropathy, where the genetic and autoimmune dependency remains poorly characterized. OBJECTIVE: To investigate autoimmune and immunogenetic aspects of ON. METHOD: In a prospective population-based cohort 51 patients with ON were included. At follow up 20 patients had progressed to multiple sclerosis (MS-ON). All patients were screened for neuronal and systemic autoantibodies. HLA genotypes and allele and genotype frequencies of the PTPN22 C1858T and the PD-1.3 single-nucleotide polymorphisms (SNPs) were determined and compared to a cohort of Danish blood donors, acting as healthy controls. RESULTS: Median follow-up was 366 days (301-430) for MS-ON patients and 375 (range 50-436) for isolated ON (ION). Autoantibodies against myelin oligodendrocyte glycoprotein (MOG-IgG), were positive in two patients, no patients had anti-aquaporin-4 antibodies. Coexisting neural autoantibodies were detected in two patients and in 12 patients other systemic autoantibodies were found. Four (8%) had other autoimmune disorders. A family history of autoimmunity was observed in 12 (24%) and of demyelinating disease in six patients (12%). In MS-ON patients the frequencies of HLA-DQB1*06:02 and HLA-DRB1*15:01 tended to be higher compared to controls (p = 0.08). Stratification of patients with presence of oligoclonal bands (OCB) showed an association to the HLA-DQB1*06:02-HLA-DRB1*15:01 haplotype in ION (HLA-DQB1*06:02 and HLA-DRB1*15:01 (p = 0.03)), and in MS-ON patients (HLA-DQB1*06:02 and HLA-DRB1*15:01 (p = 0.03)). No significant associations to PTPN22 1858C/T or PD-1.3 G/A were found in any group comparison. CONCLUSIONS: ON patients had a general susceptibility to autoimmunity and two were MOG-IgG positive. HLA-DQB1*06:02 and HLA-DRB1*15:01 were associated with the presence of OCB in ON patients.

MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature.

BACKGROUND: Antibodies to human full-length myelin oligodendrocyte glycoprotein (MOG-IgG) as detected by new-generation cell-based assays have recently been described in patients presenting with acute demyelinating disease of the central nervous system, including patients previously diagnosed with multiple sclerosis (MS). However, only limited data are available on the relevance of MOG-IgG testing in patients with chronic progressive demyelinating disease. It is unclear if patients with primary progressive MS (PPMS) or secondary progressive MS (SPMS) should routinely be tested for MOG-IgG. OBJECTIVE: To evaluate the frequency of MOG-IgG among patients classified as having PPMS or SPMS based on current diagnostic criteria. METHODS: For this purpose, we retrospectively tested serum samples of 200 patients with PPMS or SPMS for MOG-IgG using cell-based assays. In addition, we performed a review of the entire English language literature on MOG-IgG published between 2011 and 2017. RESULTS: None of 139 PPMS and 61 SPMS patients tested was positive for MOG-IgG. Based on a review of the literature, we identified 35 further MOG-IgG tests in patients with PPMS and 55 in patients with SPMS; the only reportedly positive sample was positive just at threshold level and was tested in a non-IgG-specific assay. In total, a single borderline positive result was observed among 290 tests. CONCLUSION: Our data suggest that MOG-IgG is absent or extremely rare among patients with PPMS or SPMS. Routine screening of patients with typical PPMS/SPMS for MOG-IgG seems not to be justified.

A population-based prospective study of optic neuritis.

BACKGROUND: Optic neuritis (ON) is often associated with multiple sclerosis (MS). Early diagnosis is critical to optimal patient management. OBJECTIVE: To estimate the incidence of acute ON and the rates of conversion to MS and antibody-mediated ON. METHOD: Population-based prospective study was performed in patients with ON from three ophthalmological departments and 44 practicing ophthalmologists from 2014 to 2016. Ophthalmological and neurological examination, magnetic resonance imaging (MRI), determination of aquaporin-4(AQP4)-IgG and myelin-oligodendrocyte glycoprotein (MOG)-IgG were investigated blindly. RESULTS: In all, 63 patients were evaluated and 51 fulfilled the criteria for ON. All were Caucasian, with female:male ratio of 2.2:1 and a median age of 38 years (16-66); 44 (86%) had a single episode of ON (four bilateral), while 7/51 (14%) had recurrent ON. The overall age-specific incidence was 3.28 (2.44-4.31) per 100,000 person years, 2.02 for men and 4.57 for women. At follow-up, 20 patients met the diagnostic criteria for MS, MRI lesions disseminated in space and time in 17/20 patients. AQP4-IgG was detected in none, MOG-IgG was detected in two patients. CONCLUSION: The prospective incidence of ON was estimated. MRI enabled a diagnosis of MS in a subgroup of patients. Antibody-mediated ON with specificity for MOG was detected in 4% of cases.

Myocardial edema in acute myocarditis: relationship of T2 relaxometry and late enhancement burden by using dual-contrast turbo spin-echo MRI.

To quantify myocardial edema by using a T2 relaxometry approach with a dual-contrast turbo spin-echo (dcTSE) sequence in patients with acute myocarditis regarding focal late gadolinium enhancement (LGE) burden. CMR T2 relaxometry was performed in 39 patients (age 41 ± 19 years; 36% women) with LGE in a typical myocarditis pattern and in ten healthy volunteers (age 46 ± 12; 60% woman). dcTSE sequence (echo time 29 and 75 ms, respectively) was used for T2 mapping, analysis were performed on the basis of region of interest (ROI). Myocardial T2 relaxation times (T2 RT) in patients-ROI with focal LGE were significantly (p < 0.001) higher than T2 RT in patients-ROI without apparent LGE pattern (65 ms (IQR 36-95) vs. 60 ms (IQR 26-88), respectively). T2 RT in healthy volunteers [55 ms (IQR 35-71)] were significantly lower than in patients ROI with or without focal LGE-pattern (p < 0.001, respectively). T2 RT assessed by dcTSE are significantly higher in patients segments with and without focal LGE compared to normal controls, supporting a global myocardial inflammatory process in acute myocarditis. Furthermore, this quantitative T2-mapping approach highlights the potential to identify patients with diffuse myocarditis.

Antibody biomarkers in CNS demyelinating diseases - a long and winding road.

Over several decades, studies sought potential markers to diagnose and to predict the clinical course of central nervous system (CNS) demyelinating disorders, especially in multiple sclerosis, acute disseminated encephalomyelitis and neuromyelitis optica spectrum disorders. Reliable biomarkers would ensure correct diagnoses, determine future disease evolvements, stratify patients for appropriate treatments and monitor disease activity and treatment effects - in summary, meet the longing for personalized medicine in these diseases. Out of a plethora of potential biomarker candidates antibodies have turned (again) into the scientific focus, due to pivotal immunological and neuropathological findings in the past 20 years. A major breakthrough and stimulus for further research was the identification of anti-aquaporin-4 antibodies in neuromyelitis optica. Various other myelin and non-myelin antigens were investigated in detail for diagnostic and prognostic purposes, such as antibodies to myelin oligodendrocyte glycoprotein or to the potassium channel KIR4.1. Further, the use of biopharmaceutical treatments in multiple sclerosis led to intense research activities to identify anti-treatment neutralizing antibodies and their clinical consequences. This review briefly summarizes the current knowledge on antibodies in the diagnosis, prognosis, disease and treatment monitoring of CNS demyelinating disorders.

Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibodies have been recently described in children with acute disseminating encephalomyelitis (ADEM), but the clinical and neuroradiological characterisation of this subgroup is lacking. OBJECTIVE: To compare the clinical and neuroradiological features of paediatric ADEM with and without MOG antibodies. METHODS: Clinical course, cerebrospinal fluid (CSF)-, MRI studies, outcome and MOG status of 33 paediatric ADEM prospectively studied were reviewed. RESULTS: MOG antibodies (median 1:2560; range 1:160-1:20 480) were detected in 19 children with ADEM. The majority of children showed a decline of serum MOG-IgG titres over time. Children with MOG antibodies did not differ in their age at presentation, sex ratio, the presence of oligoclonal bands, clinical symptoms or initial severity, apart from a higher CSF cell count (p=0.038), compared with children without MOG antibodies. In addition, further relapsing demyelinating episodes associated with MOG antibodies were observed only in children with MOG antibodies. All 19 children with MOG antibodies had a uniform MRI pattern, characterised by large, hazy and bilateral lesions and the absence of atypical MRI features (eg, mainly small lesions, well-defined lesions), which was significantly different compared to that of children without MOG antibodies (p=0.003; and p=0.032, respectively). In addition, children with MOG antibodies had involvement of more anatomical areas (p=0.035) including the myelon characterised by a longitudinally extensive transverse myelitis (p=0.003), more often a complete resolution of lesions (p=0.036) and a better outcome (p=0.038). CONCLUSIONS: Patients with ADEM with MOG antibodies in our cohort had a uniform MRI characterised by large, bilateral and widespread lesions with an increased frequency of longitudinal extensive transverse myelitis and a favourable clinical outcome in contrast to children lacking MOG antibodies.

TIRC7 and HLA-DR axis contributes to inflammation in multiple sclerosis.

BACKGROUND AND OBJECTIVE: Interactions between TIRC7 (a novel seven-transmembrane receptor on activated lymphocytes) and its ligand HLA-DR might be involved in the inflammatory process in multiple sclerosis (MS). METHODS: Methods comprised immunohistochemistry and microscopy on archival MS autopsies, proliferation-, cytokine-, and surface-staining assays using peripheral blood lymphocytes (PBLs) from MS patients and an in vitro model. RESULTS: TIRC7 was expressed in brain-infiltrating lymphocytes and strongly correlated with disease activity in MS. TIRC7 expression was reduced in T cells and induced in B cells in PBLs obtained from MS patients. After ex vivo activation, T cell expression of TIRC7 was restored in patients with active MS disease. The interaction of TIRC7(+) T lymphocytes with cells expressing HLA-DR on their surface led to T cell proliferation and activation whereas an anti-TIRC7 mAb preventing interactions with its ligand inhibited proliferation and Th1 and Th17 cytokine expression in T cells obtained from MS patients and in myelin basic protein-specific T cell clone. CONCLUSION: Our findings suggest that TIRC7 is involved in inflammation in MS and anti-TIRC7 mAb can prevent immune activation via selective inhibition of Th1- and Th17-associated cytokine expression. This targeting approach may become a novel treatment option for MS.

Persisting myelin oligodendrocyte glycoprotein antibodies in aquaporin-4 antibody negative pediatric neuromyelitis optica.

BACKGROUND: Recently we showed that antibodies to myelin oligodendrocyte glycoprotein (MOG) can be found in aquaporin-4 (AQP4)-immunoglobulin (IgG) seronegative pediatric and adult patients with definite and high-risk neuromyelitis optica (NMO). OBJECTIVE: The purpose of this study was to describe the clinical characteristics and temporal dynamics of MOG-IgG in AQP4-IgG seronegative pediatric patients presenting with definite NMO. METHODS: Children with definite NMO who were referred for further testing of serum antibodies for AQP4 and MOG with a cell-based assay were included in this study. Clinical disease course, cerebrospinal fluid and magnetic resonance imaging (MRI) studies of these patients were reviewed. RESULTS: Between 2008 and 2012 eight children who fulfilled the diagnostic criteria of definite NMO were recruited. Two children with definite NMO tested positive for AQP4-IgG but were negative for MOG-IgG antibodies. Three children had an absence of AQP4-IgG and MOG-IgG antibodies. Three children with definite NMO had high titers of serum MOG-IgG antibodies (≥1: 160), but no AQP4-directed humoral immune response. Longitudinal analysis of serum samples of the latter three children showed persisting high MOG-IgG titers over time. CONCLUSION: Pediatric patients presenting with clinical symptoms and MRI findings highly suggestive of NMO but with high and persisting MOG-IgG antibody titers are most likely to represent a distinct subgroup of acute demyelinating diseases with important clinical and therapeutic implications.

Development of a mirror-based endoscope for divertor spectroscopy on JET with the new ITER-like wall (invited).

A new endoscope with optimised divertor view has been developed in order to survey and monitor the emission of specific impurities such as tungsten and the remaining carbon as well as beryllium in the tungsten divertor of JET after the implementation of the ITER-like wall in 2011. The endoscope is a prototype for testing an ITER relevant design concept based on reflective optics only. It may be subject to high neutron fluxes as expected in ITER. The operating wavelength range, from 390 nm to 2500 nm, allows the measurements of the emission of all expected impurities (W I, Be II, C I, C II, C III) with high optical transmittance (≥ 30% in the designed wavelength range) as well as high spatial resolution that is ≤ 2 mm at the object plane and ≤ 3 mm for the full depth of field (± 0.7 m). The new optical design includes options for in situ calibration of the endoscope transmittance during the experimental campaign, which allows the continuous tracing of possible transmittance degradation with time due to impurity deposition and erosion by fast neutral particles. In parallel to the new optical design, a new type of possibly ITER relevant shutter system based on pneumatic techniques has been developed and integrated into the endoscope head. The endoscope is equipped with four digital CCD cameras, each combined with two filter wheels for narrow band interference and neutral density filters. Additionally, two protection cameras in the λ > 0.95 µm range have been integrated in the optical design for the real time wall protection during the plasma operation of JET.

Olfactory threshold is impaired in early, active multiple sclerosis.

BACKGROUND: Olfactory dysfunction has been reported in multiple sclerosis (MS). However, to date no data are available on different qualities of olfactory function, namely odour identification, odour discrimination and odour perception threshold. OBJECTIVE: To assess different qualities of olfactory function in patients with MS and correlate these with demographic data, clinical data, depression, quality of life and cognitive functions. METHODS: In this cross-sectional study, 50 patients with MS or clinically isolated syndrome and 30 healthy controls were included. Olfactory function was measured using the Sniffin' Sticks test. RESULTS: The scores for odour identification (p = 0.001), odour perception threshold (p = 0.037) and the combined score of odour identification, discrimination and perception threshold (TDI, p = 0.002) were significantly lower in MS. Hyposmia for identification (p = 0.0017), threshold (p = 0.017) and TDI score (p = 0.0014) was more frequent in MS. Olfactory threshold was impaired in patients who were clinically active in the previous year (p = 0.026) and in patients with a disease duration less than 2 years (p = 0.0093). Identification score was negatively correlated with disease duration (p = 0.0017). Olfactory function was not associated with disability, depression or quality of life. CONCLUSIONS: We report evidence for qualitatively distinct hyposmia in MS, with increased smell threshold in the early inflammatory phases of the disease and impaired identification with a more widespread chronic disease.

Targeting the Nogo receptor complex in diseases of the central nervous system.

After injury to the central nervous system intrinsic factors such as myelin associated inhibitory factors inhibit cellular and axonal regeneration resulting in permanent disability. Three of these factors (Nogo-A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein) bind to a common receptor: the Nogo-66 receptor (NgR1). NgR1 is expressed mainly on neurons and is usually associated in a trimolecular complex. The second member of the complex, LINGO-1, is often connected to NgR1 function and is further found to function independently as a negative regulator of oligodendrocyte proliferation and differentiation. The third member of the NgR complex is either the p75 neurotrophin receptor, TROY, or an as yet unidentified co-receptor. Targeting of factors contained in this complex has been described to lead to the promotion of neurite outgrowth, oligodendrocyte proliferation and differentiation and inhibition of cell death. In the current review, we aim to describe the mechanisms of action of the chemical and biological compounds used in targeting NgR1 and LINGO-1. This will be achieved using three examples: blocking of ligand binding to NgR1 in treatment of spinal cord injury, antibody-mediated inhibition of LINGO-1 to promote oligodendrocyte differentiation in multiple sclerosis, and the use of soluble NgR1 to sequester Abeta peptide in the periphery in Alzheimer's disease.

Fine mapping of T-cell immunoglobulin mucin domain gene 1 failed to detect a significant association with multiple sclerosis.

The T-cell immunoglobulin mucin (TIM) gene family encodes receptors on T-cells that regulate Th1- and Th2-cell-mediated immunity. Recently published data implied differential expression of human TIM molecules by mononuclear cells in cerebrospinal fluid of patients with multiple sclerosis (MS) and might therefore be involved in different phases of the pathogenesis of MS. The purpose of this study was to investigate the association of TIM1 gene polymorphism with susceptibility to and clinical progression in MS. In total, 272 patients with MS and 272 sex- and age-matched healthy blood donors from Western Austria were genotyped for 10 single nucleotide polymorphisms (SNPs). Five SNPs were located in the promoter region of TIM1 (rs7702920, rs41297577, rs41297579, rs9313422 and rs34333511). Another five SNPs were selected in exon 4 (rs1553316 and rs12522248) and in the intronic regions 4 and 7 of TIM1 (rs1553318, rs2279804 and rs2277025), respectively. None of these SNPs showed a significant association with MS after correction for multiple comparisons. Haplotype analysis of our data resulted in 11 haplotypes and showed no significant differences between MS patients and controls. Our findings suggest that even fine mapping of TIM1 shows no significant association of this gene with multiple sclerosis.

Real-time sonoelastography: findings in patients with symptomatic achilles tendons and comparison to healthy volunteers.

PURPOSE: Real-time sonoelastography (SE), a newly introduced ultrasound technique, has already shown conclusive results in breast, prostate, and thyroid tumor diagnostics. This study investigated the performance of SE for the differentiation of Achilles tendon alterations of tendinopathy compared to clinical examination and conventional ultrasound (US). MATERIALS AND METHODS: Achilles tendons in 25 consecutive patients with chronic Achilles tendinopathy and 25 healthy volunteers were examined clinically by US and by SE. RESULTS: In the healthy volunteers, SE showed the tendon to be hard (93 %), while distinct softening was found in 57 % of the patients. SE showed more frequent involvement of the distal (64 %) and middle third (80 %) than the proximal third (28 %) of the Achilles tendon. Using SE a mean sensitivity of 94 %, specificity of 99 %, and accuracy of 97 % were found when clinical examination was used as the reference standard. The correlation to US was 0.89. Mild softening was found in 7 % of the healthy volunteers and in 11 % of the patients. CONCLUSION: Our results emphasize that only distinct softening of Achilles tendons is comparable to clinical examination and US findings. However, mild softening might be explained by very early changes in tissue elasticity in the case of Achilles tendinopathy, which should be assessed in follow-up studies.

Monoclonal antibodies in the treatment of multiple sclerosis.

Multiple sclerosis (MS), a chronic demyelinating disorder, is characterized by recurrent neurological deficits or progressive impairment with a high risk of permanent disability. Since the exact pathophysiology and etiology remains still unclear, no curing therapy is currently available. However, several treatments with beneficial effect on relapse rate such as the first line therapies interferon-beta and glatiramer acetate were approved for relapsing-remitting MS. One new important tool in the therapy of MS is the use of monoclonal antibodies. Natalizumab is the first and so far only monoclonal antibody that is approved for MS treatment by the US Food and Drug Administration and the European Medicines Agency. In addition to natalizumab other monoclonal antibodies previously used in cancer and other autoimmune disorders or even newly developed for MS are now being tested in clinical trials. With their high target specificity and efficacy monoclonal antibodies are a promising treatment approach in MS. This review summarizes the present knowledge on the use, effectiveness and safety of monoclonal antibodies in MS treatment.