Papers by Harry Alexopoulos
Trends in Molecular Medicine
Stiff person syndrome (SPS) is a highly-disabling neurological disorder of the CNS characterized ... more Stiff person syndrome (SPS) is a highly-disabling neurological disorder of the CNS characterized by progressive muscular rigidity and spasms. In approximately 60–80 % of patients there are autoantibodies to glutamic acid decarboxylase (GAD), the enzyme that synthesizes gamma-amino butyric acid (GABA), the predominant inhibitory neurotransmitter of the CNS. Although GAD is intracellular, it is thought that autoimmunity to GAD65 may play a role in the development of SPS. To test this hypothesis, we immunized mice, that expressed enhanced green fluorescent protein (EGFP) under the GAD65 promoter, with either GAD65 (n = 13) or phosphate buffered saline (PBS) (n = 13). Immunization with GAD65 resulted in autoantibodies that immunoprecipitated GAD, bound to CNS tissue in a highly characteristic pattern, and surprisingly bound not only to GAD intracellularly but also to the surface of cerebellar neurons in culture. Moreover, immunization resulted in immunoglobulin diffusion into the brains...
Neurology, 2016
OBJECTIVE: To describe the clinical and immunological characteristics of a case series with post-... more OBJECTIVE: To describe the clinical and immunological characteristics of a case series with post-HSV autoimmune encephalitis. BACKGROUND: Autoimmune encephalitides are diseases of children and adults associated with autoantibodies against synaptic antigens. They present with a variety of symptoms, including psychosis, cognitive and memory disrurbances, seizures and abnormal movements. It has been recently reported that HSV can trigger brain autoimmunity, as up to 20[percnt] of patients with HSV-encephalitis relapse, developing autoimmune NMDAR encephalitis. METHODS: Patient sera and CSF were tested for anti-NMDAR, GABAbR, AMPAR, LGI1, CASPR2 and DDPX antibodies using cell-based assays. RESULTS: Three patients developed autoimmune-encephalitis following HSV-encephalitis. A 33 year-old woman continued having symptoms after 2 weeks of anti-HSV therapy and developed anti-NMDAR antibodies in serum, and anti-GABAbR antibodies in both serum and CSF. Following immunotherapy, she fully recov...
OBJECTIVE: To assess whether the improvement seen after intravenous immunoglobulin (IVIg) therapy... more OBJECTIVE: To assess whether the improvement seen after intravenous immunoglobulin (IVIg) therapy in patients with Stiff Person Syndrome (SPS), an antibody-mediated disease model, is related to shifting epitope recognition of the anti-glutamic acid decarboxylase (GAD65) antibodies. BACKGROUND: IVIg is an effective therapy in patients with SPS based on a placebo-controlled randomized trial (Dalakas et al, NEJM, 2001). SPS patients harbor high-titer antibodies against GAD65, the enzyme that converts glutamic acid into GABA. Previous epitope mapping studies have shown that in SPS patients these antibodies bind predominantly to the enzyme’s catalytic domain and inhibit its action. DESIGN/METHODS: An immunoprecipitation assay (LIPS) was used for epitope mapping. Full length and three non-overlapping fragments of GAD65, spanning amino-acids 2-95 (GAD65D1), 96-444 (GAD65D2) and 445-585 (GAD65D3), were cloned next to a luciferase reporter gene (RUC). A sub-fragment of the GAD65D2 domain, sp...
Objective: To examine whether CIDP patients harbour antibodies against antigens expressed at the ... more Objective: To examine whether CIDP patients harbour antibodies against antigens expressed at the nodes of Ranvier such as contactin-2/TAG1 and connexin 32 (Cx32). Introduction: Nodal, paranodal and juxtaparanodal proteins have been the focus of ongoing research as potential antigens in both central and peripheral demyelinating disorders. Antibodies against contactin-2, which plays a role in the formation of axonal connections, have been detected in multiple sclerosis patients (Derfuss et al, PNAS 2009; 106, 8302) and polymorphisms in the gene encoding contactin-2 may influence treatment response in CIDP (Iijima et al, Neurology 2009; 73, 1348). Cx32, which comprises gap junctions of the paranode, is also a potential target antigen in PNS demyelination (Dalakas, Nat Rev Neurol 2011; 7, 507) as mutations in Cx32 cause Charcot-Marie-Tooth disease. Patients/methods: Sera from 45 patients with CIDP (with paired CSF samples from two), 5 with multifocal motor neuropathy (MMN), and 4 with c...
OBJECTIVE: To describe the association of new autoantibodies with cerebellar ataxia. BACKGROUND: ... more OBJECTIVE: To describe the association of new autoantibodies with cerebellar ataxia. BACKGROUND: Several new autoantibodies associated with neurological disorders have been identified in recent years, including antibodies for cerebellar ataxia. Apart from the typical paraneoplastic anti-Yo antibodies, a small number of patients have also antibodies against GAD as well as antibodies against Purkinje cell antigens such as mGluR1, Homer-3 and anti Tr/DNER. DESIGN/METHODS: We first screened 15 patients with cerebellar ataxia and no other known associated autoantibodies with immunocytochemistry on mouse brain slices. One patient showed a distinct staining pattern on Purkinje neuronal dendrites and was further investigated by immunoprecipitation, protein electrophoresis and mass spectrometry. These studies identified the autoantigen as the inositol 1,4,5-triphosphate receptor 1 (IP3R1), an intracellular Ca2+ channel that mediates the release of Ca2+ from intracellular stores. We then deve...
Neurology, 2018
Objective: To determine whether in SPS, CSF anti-GAD antibodies correlate with clinical severity ... more Objective: To determine whether in SPS, CSF anti-GAD antibodies correlate with clinical severity and disease progression. Background: SPS is a naturally progressive disorder, characterized by muscle rigidity and episodic spasms in axial and limb musculature, along with heightened sensitivity to external stimuli. SPS is associated with high titer anti-GAD antibodies in both serum and CSF. Design/Methods: CSF was examined for anti-GAD antibodies and intrathecal GAD-specific IgG synthesis in 32 typical SPS patients and 5 patients with SPS and cerebellar disease (SPS-Cer). Anti-GAD antibodies were also measured in serial CSF samples (first and 2-year visits) in 10 patients not receiving immunotherapy. Results: In the 32 SPS patients, the GAD CSF-titers ranged from 30–2,000 Standard Units (mean, 280; normal 0). The mean titer ratio of anti-GAD CSF/serum was 0.01 and the mean ratio of CSF/serum IgG was 0.002 indicating a 4-fold increase of intrathecal GAD-IgG specific production. In the S...
Therapeutic Advances in Neurological Disorders, 2021
Antibodies against glutamic acid decarboxylase (GAD), originally linked to stiff person syndrome ... more Antibodies against glutamic acid decarboxylase (GAD), originally linked to stiff person syndrome (SPS), now denote the “ GAD antibody-spectrum disorders” ( GAD-SD) that also include autoimmune epilepsy, limbic encephalitis, cerebellar ataxia and nystagmus with overlapping symptomatology highlighting autoimmune neuronal excitability disorders. The reasons for the clinical heterogeneity among GAD-antibody associated syndromes remain still unsettled, implicating variable susceptibility of GABAergic neurons to anti-GAD or other still unidentified autoantibodies. Although anti-GAD antibody titers do not correlate with clinical severity, very high serum titers, often associated with intrathecal synthesis of anti-GAD-specific IgG, point to in-situ effects of GAD or related autoantibodies within the central nervous system. It remains, however, uncertain what drives these antibodies, why they persist and whether they are disease markers or have pathogenic potential. The review, focused on th...
The Lancet Neurology, 2021
Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified ... more Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder that presents in both adults and children as CNS demyelination. Although there are clinical phenotypic overlaps between MOGAD, multiple sclerosis, and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (NMOSD) cumulative biological, clinical, and pathological evidence discriminates between these conditions. Patients should not be diagnosed with multiple sclerosis or NMOSD if they have anti-MOG antibodies in their serum. However, many questions related to the clinical characterisation of MOGAD and pathogenetic role of MOG antibodies are still unanswered. Furthermore, therapy is mainly based on standard protocols for aquaporin-4 antibody-associated NMOSD and multiple sclerosis, and more evidence is needed regarding how and when to treat patients with MOGAD.
Neurology - Neuroimmunology Neuroinflammation, 2020
ObjectiveTo investigate the pathophysiologic mechanism of encephalopathy and prolonged comatose o... more ObjectiveTo investigate the pathophysiologic mechanism of encephalopathy and prolonged comatose or stuporous state in severally ill patients with coronavirus disease 2019 (COVID-19).MethodsEight COVID-19 patients with signs of encephalopathy were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the serum and CSF using a Food and Drug Administration-approved and independently validated ELISA. Blood-brain barrier (BBB) integrity and immunoglobulin G (IgG) intrathecal synthesis were further tested using albumin and IgG indices. The CSF was also tested for autoimmune encephalitis antibodies and 14-3-3, a marker of ongoing neurodegeneration.ResultsAll patients had anti–SARS-CoV-2 antibodies in their CSF, and 4 of 8 patients had high titers, comparable to high serum values. One patient had anti–SARS-CoV-2 IgG intrathecal synthesis, and 3 others had disruption of the blood-brain barrier. The CSF in 4 patients was positive for 14-3-3-protein suggestin...
Nature Reviews Neurology, 2020
The human complement system is an effector of innate and adaptive humoral immunity. The system co... more The human complement system is an effector of innate and adaptive humoral immunity. The system comprises soluble membrane-bound proteins (opsonins) that act collectively to recognize pathogens and non-self material and subsequently initiate opsonization and phagocytosis or lysis of pathogens. The proteolytic fragments that derive from complement activation can be targeted by white blood cells and endothelial cells, leading to extravasation and migration of immune cells at the sites of inflammation. Other physiological functions of complement include timely removal of altered and senescent self, tissue remodelling, cell lysis, chemotaxis, opsonization, inflammation and immune cell stimulation 1-4. Complement activation products link the innate and adaptive immune systems by acting directly on receptors on T cells and B cells or by modulating dendritic cell functions 5-8. Disruption of the delicate coordination required for complement activation and control is fundamental in the pathogenic mechanism of several autoimmune neurological disorders, and is even emerging as a contributor in some neurodegenerative diseases. As a result, interest is increasing in targeting complement as a therapeutic approach to prevent ongoing tissue destruction in several difficult-to-treat neurological diseases. In this Review, we provide an overview of the main components of the initial complement activation pathways, the lytic pathway and the factors associated with inappropriate complement activation or control in disease initiation and progression. We consider the role of complement in the tissue destruction that is responsible for the genesis of the most common autoimmune neurological diseases, including complement-mediated myopathies, myasthenia gravis, neuropathies and CNS disorders. We also discuss the role of complement in some neurodegenerative disorders, including Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS), Huntington disease, traumatic brain injury and even schizophrenia. Finally, we discuss emerging complement-targeted therapies, such as monoclonal antibodies, fusion proteins and cyclic peptides, that inhibit the functions of individual complement proteins, especially therapies that disrupt the lytic pathway. Some of these therapeutic agents have been approved or are being tested in phase I-III clinical trials and promise to change the therapeutic armamentarium for treatment of neurological conditions that respond poorly to existing immunotherapies.
Journal of Autoimmunity, 2019
Autoimmune encephalitides, with an estimated incidence of 1.5 per million population per year, al... more Autoimmune encephalitides, with an estimated incidence of 1.5 per million population per year, although described only 15 years ago, have already had a remarkable impact in neurology and paved the field to autoimmune neuropsychiatry. Many patients traditionally presented with aberrant behavior, especially of acute or subacute onset, and treated with anti-psychotic therapies, turn out to have a CNS autoimmune disease with pathogenic autoantibodies against synaptic antigens responding to immunotherapies. The review describes the clinical spectrum of these disorders, and the pathogenetic role of key autoantibodies directed against: a) cell surface synaptic antigens and receptors, including NMDAR, GABAa, GABAb, AMPA and glycine receptors; b) channels such as AQP4 water-permeable channel or voltage-gated potassium channels; c) proteins that stabilize voltage-gated potassium channel complex into the membrane, like the LGI1 and CASPR2; and d) enzymes that catalyze the formation of neurotransmitters such as Glutamic Acid Decarboxylase (GAD). These antibodies, effectively target excitatory or inhibitory synapses in the limbic system, basal ganglia or brainstem altering synaptic function and resulting in uncontrolled neurological excitability disorder clinically manifested with psychosis, agitation, behavioral alterations, depression, sleep disturbances, seizure-like phenomena, movement disorders such as ataxia, chorea and dystonia, memory changes or coma. Some of the identified triggering factors include: viruses, especially herpes simplex, accounting for the majority of relapses occurring after viral encephalitis, which respond to immunotherapy rather than antiviral agents; tumors especially teratoma, SCLC and thymomas; and biological cancer therapies (immune-check-point inhibitors). As anti-synaptic antibodies persist after viral infections or tumor removal, augmentation of autoreactive B cells which release autoantigens to draining lymph nodes, molecular mimicry and infection-induced bystander immune activation products play a role in autoimmunization process or perpetuating autoimmune neuroinflammation. The review stresses the importance of early detection, clinical recognition, proper antibody testing and early therapy initiation as these disorders, regardless of a known or not trigger, are potentially treatable responding to systemic immunotherapy with intravenous steroids, IVIg, rituximab or even bortezomid.
Therapeutic advances in neurological disorders, 2018
Recent evidence suggests that patients with herpes simplex virus (HSV) encephalitis may relapse b... more Recent evidence suggests that patients with herpes simplex virus (HSV) encephalitis may relapse because of autoimmunity against the N-methyl-D-aspartate receptor (NMDAR). We present a case series of post-HSV relapsing encephalopathy associated with antibodies to central nervous system (CNS) synaptic antigens. Sera and cerebrospinal fluid (CSF) from five patients with HSV encephalitis who relapsed after antiviral therapy were tested for anti-NMDAR, gamma-aminobutyric acid b receptor (GABAbR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), Leucine-rich, glioma inactivated 1 (LGI1), anti -contactin-associated protein-like 2 (CASPR2) and dipeptidyl-peptidase-like protein-6 (DDPX) antibodies using cell-based assays. Five patients (two infants, one child and two adults) developed post-HSV autoimmune encephalitis. The infants, aged 9 months and 10 months, after prompt and seemingly successful anti-HSV therapy, were readmitted with typical signs of NMDAR-encephalitis...
Annals of Neurology, 2017
In Stiff-Person Syndrome (SPS), an antibody-mediated impaired GABAergic neurotransmission is beli... more In Stiff-Person Syndrome (SPS), an antibody-mediated impaired GABAergic neurotransmission is believed to cause muscle stiffness and spasms. Patients improve with GABA-enhancing drugs and IVIg, but several respond poorly and remain disabled. The need for more effective therapy prompted a trial with the anti-CD20 monoclonal antibody rituximab. Methods This was a placebo-controlled randomized trial of rituximab (two biweekly infusions of 1gr each). The primary outcome was a change in stiffness scores at 6 months. Secondary outcomes were changes in heightened-sensitivity and quality of life scores. Enrolling 24 patients was calculated to detect 50% change in stiffness scores. Results Randomization was balanced for age, sex, disease duration and GAD autoantibody titers. No significant changes were noted at 6 months after treatment in all outcomes. Specifically, no differences were noted in the stiffness index, the primary outcome, or sensitivity scores, the secondary outcome, at 3 or 6 months. Quality of life scores improved significantly (p<0.01) at 3 months in both groups, but not at 6 months, denoting an early placebo effect. Blinded self-assessment rating of the overall stiffness for individual patients revealed improvement in four patients in each group. At 6 months, improvement persisted in one patient in the placebo group vs. three out of 4 in the rituximab group, where these meaningful improvements were also captured by video recordings. Interpretation This is the largest controlled trial conducted in SPS patients demonstrating no statistically significant difference in the efficacy measures between rituximab and placebo. The lack of rituximab's efficacy could be due to a considerable placebo effect; insensitivity of scales to quantify stiffness especially in the less severely affected patients; or drug effectiveness only in a small patient subset.
Neurology - Neuroimmunology Neuroinflammation, 2016
Objective:To describe newly identified autoantibodies associated with cerebellar disorders.Design... more Objective:To describe newly identified autoantibodies associated with cerebellar disorders.Design/Methods:We first screened the sera of 15 patients with cerebellar ataxia, without any known associated autoantibodies, with immunocytochemistry on mouse brain. After characterization and validation of a newly identified antibody, 85 additional patients with suspected autoimmune cerebellar disease were screened using a cell-based assay.Results:Immunoglobulin G from one of the first 15 patients demonstrated a distinct staining pattern on Purkinje neurons. This autoantibody, as characterized further by immunoprecipitation and mass spectrometry, was binding inositol 1,4,5-triphosphate receptor 1 (IP3R1), an intracellular channel that mediates the release of Ca2+ from intracellular stores. Anti-IP3R1 specificity was then validated with a cell-based assay. On this basis, screening of 85 other patients with cerebellar disease revealed 2 additional IP3R1-positive patients. All 3 patients presen...
Neurology, Apr 6, 2015
Objective: To investigate patients with recurrent optic neuritis (rON) for anti-MOG antibodies. B... more Objective: To investigate patients with recurrent optic neuritis (rON) for anti-MOG antibodies. Background: Autoantibodies to myelin oligodendrocyte glycoprotein (MOG) have been identified in some patients with inflammatory demyelinating diseases including pediatric multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM) and AQP4-seronegative NMO spectrum disorders (NMOSD). rON refers to a clinically distinct subset of patients, thought to fall within the rubric of NMODS. These patients characteristically exhibit several steroid-sensitive episodes of optic neuritis (ON) and do not develop spinal cord symptomatology. Methods: We examined sera from 111 AQP4-negative patients with clinical features of either multiple sclerosis or NMOSD using a cell-based assay, which detects structural and extracellular anti-MOG epitopes. Screening was performed with human embryonic kidney cells, transiently transfected with MOG C-terminally fused to EGFP. Results: Anti-MOG antibodies were detected in 8 patients with ON; 5 of them were diagnosed as definite rON because they had 蠅3 episodes of ON without any other clinical symptomatology. Brain/orbital MRI or CSF analyses (when available) were normal except for optic nerve enhancement in two of them. Spinal cord MRI depicted a small subclinical chronic lesion in the cervical spine in one of 8 patients who never developed clinical symptoms of myelitis during our follow-up period. All anti-MOG-positive patients were steroid responsive but two of them, required other immunosuppressants, plasmapheresis or IVIG to suppress or prevent relapses. Conclusion: Patients with the clinically distinct entity of rON (AQP4-negative) are characterized by antibodies against MOG. Because anti-MOG antibodies have been also detected in typical NMOSD (either AQP4-negative or AQP4-positive), different MOG epitopes may distinguish rON from NMOSD. Whether in rON patients the anti-MOG antibodies are causally connected to conduction block in the optic nerve or demyelination is unclear. The pathogenicity of these antibodies is currently explored on optic nerve ex vivo preparations in our laboratory. Disclosure: Dr. Chalmoukou has nothing to disclose. Dr. Stathopoulos has nothing to disclose. Dr. Alexopoulos has nothing to disclose. Dr. Akrivou has nothing to disclose. Dr. Dalakas has received personal compensation for activities with Baxter, Novartis, Grifols, CSL, Octapharma, Dysimmune Diseases Foundation, and Therapath. Dr. Dalakas has received personal compensation in an editorial capacity for Therapeutic Advances i
Neurology, Apr 8, 2014
Objective: To examine whether CIDP patients harbour antibodies against antigens expressed at the ... more Objective: To examine whether CIDP patients harbour antibodies against antigens expressed at the nodes of Ranvier such as contactin-2/TAG1 and connexin 32 (Cx32). Introduction: Nodal, paranodal and juxtaparanodal proteins have been the focus of ongoing research as potential antigens in both central and peripheral demyelinating disorders. Antibodies against contactin-2, which plays a role in the formation of axonal connections, have been detected in multiple sclerosis patients (Derfuss et al, PNAS 2009; 106, 8302) and polymorphisms in the gene encoding contactin-2 may influence treatment response in CIDP (Iijima et al, Neurology 2009; 73, 1348). Cx32, which comprises gap junctions of the paranode, is also a potential target antigen in PNS demyelination (Dalakas, Nat Rev Neurol 2011; 7, 507) as mutations in Cx32 cause Charcot-Marie-Tooth disease. Patients/methods: Sera from 45 patients with CIDP (with paired CSF samples from two), 5 with multifocal motor neuropathy (MMN), and 4 with combined CIDP and central demyelination (with paired CSF from one) were examined. We established a cell-based assay (CBA), in which human embryonic kidney cells were transfected with cDNA clones encoding either the FNIII or the IgC2 domains of TAG-1 or CX32, all tagged with eGFP. Antibodies against IgC2 and human Cx32 were used as positive controls. Antibody binding was visualized using an anti-human fluorescent secondary antibody. Results: No positive staining was detected in any of the patients with autoimmune peripheral neuropathies for both antigens. Conclusion: Contactin-2 and Cx32, which is responsible for a genetic demyelinating neuropathy, are not autoantibody targets in aquired autoimmune demyelinating neuropathies. Reactivity to other nodal, paranodal or juxtaparanodal antigens is currently explored. Study Supported by: Special Research Account, University of Athens Disclosure: Dr. Stathopoulos has nothing to disclose. Dr. Alexopoulos has nothing to disclose. Dr. Biba has nothing to disclose. Dr. Karagogeos has nothing to disclose. Dr. Dalakas has received personal compensation for activities with Baxter, Novartis, Grifols, CSL, Octapharma, Dysimmune Diseases Foundation, and Therapath. Dr. Dalakas has received personal compensation in an editorial capacity for Therapeutic Advances in Neurological Disorders. Dr. Dalakas has received research support from Biogen Idec, Serono, Inc., Novartis, CSL and Teva Neuroscience.
Neurology, Apr 8, 2014
OBJECTIVE: To assess whether the improvement seen after intravenous immunoglobulin (IVIg) therapy... more OBJECTIVE: To assess whether the improvement seen after intravenous immunoglobulin (IVIg) therapy in patients with Stiff Person Syndrome (SPS), an antibody-mediated disease model, is related to shifting epitope recognition of the anti-glutamic acid decarboxylase (GAD65) antibodies. BACKGROUND: IVIg is an effective therapy in patients with SPS based on a placebo-controlled randomized trial (Dalakas et al, NEJM, 2001). SPS patients harbor high-titer antibodies against GAD65, the enzyme that converts glutamic acid into GABA. Previous epitope mapping studies have shown that in SPS patients these antibodies bind predominantly to the enzyme’s catalytic domain and inhibit its action. DESIGN/METHODS: An immunoprecipitation assay (LIPS) was used for epitope mapping. Full length and three non-overlapping fragments of GAD65, spanning amino-acids 2-95 (GAD65D1), 96-444 (GAD65D2) and 445-585 (GAD65D3), were cloned next to a luciferase reporter gene (RUC). A sub-fragment of the GAD65D2 domain, spanning amino-acids 221-444 (GAD65D4) more tightly matching the catalytic core was also cloned. After construct transfection into HEK293T cells, extracts containing the RUC-antigen fusions were prepared. Sera from six SPS patients treated with IVIg (1 dose/month for three months) before and after the three-month treatment period, were incubated with extracts and antibody-antigen binding was measured by means of light emission. RESULTS: 5/6 pre-therapy SPS sera showed highest reactivity against the catalytic epitope fragments GAD65D2 and GAD65D4; one patient’s serum showed highest reactivity with fragments GAD65D1 and GAD65D2. The GAD antibody titers decreased after IVIg therapy in 3 of the 6 patients, but no differences in epitope specificity were detected in any of the 6 patients, in spite of good clinical response to IVIg. CONCLUSIONS: In GAD-positive SPS patients, IVIg does not seem to modify the GAD epitope-binding pattern even in those patients who improve after therapy. The study has implications in understanding the mode of action of IVIg in other antibody-mediated neurological conditions. Co-financed by EU and Greek funds; "Education and Lifelong Learning": Thales. Investing in knowledge society through the European Social Fund. Disclosure: Dr. Fouka has nothing to disclose. Dr. Alexopoulos has nothing to disclose. Dr. Politis has nothing to disclose. Dr. Dalakas has received personal compensation for activities with Baxter, Novartis, Grifols, CSL, Octapharma, Dysimmune Diseases Foundation, and Therapath. Dr. Dalakas has received personal compensation in an editorial capacity for Therapeutic Advances in Neurological Disorders. Dr. Dalakas has received research support from Biogen Idec, Serono, Inc., Novartis, CSL and Teva Neuroscience.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, Jan 13, 2015
B cells have an ever-increasing role in the etiopathology of a number of autoimmune neurological ... more B cells have an ever-increasing role in the etiopathology of a number of autoimmune neurological disorders, acting as antibody-producing cells and, most importantly, as sensors, coordinators, and regulators of the immune response. B cells, among other functions, regulate the T-cell activation process through their participation in antigen presentation and production of cytokines. The availability of monoclonal antibodies or fusion proteins against B-cell surface molecules or B-cell trophic factors bestows a rational approach for treating autoimmune neurological disorders, even when T cells are the main effector cells. This review summarizes basic aspects of B-cell biology, discusses the role(s) of B cells in neurological autoimmunity, and presents anti-B-cell drugs that are either currently on the market or are expected to be available in the near future for treating neurological autoimmune disorders.
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Papers by Harry Alexopoulos