Full Text Journal Articles by
Author Sarosh R Irani

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Distinctive binding properties of human monoclonal LGI1 autoantibodies determine pathogenic mechanisms.

Melanie Ramberger, Antonio Berretta, Jeanne M M Tan, Bo Sun, Sophia Michael, Tianrong Yeo, Jakob Theorell, Rachael Bashford-Rogers, Sofija Paneva, Victoria O'Dowd, Neesha Dedi, Sarfaraj Topia, Robert Griffin, Jorge Ramirez-Franco, Oussama El Far, Stéphanie Baulac, Maria I Leite, Arjune Sen, Alexander Jeans, David McMillan, Diane Marshall, Daniel Anthony, Daniel Lightwood, Patrick Waters, Sarosh R Irani,

Autoantibodies against leucine-rich glioma inactivated 1 (LGI1) are found in patients with limbic encephalitis and focal seizures. Here, we generate patient-derived monoclonal antibodies (mAbs) against LGI1. We explore their sequences and binding characteristics, plus their pathogenic potential using transfected HEK293T cells, rodent neuronal preparations, and behavioural and electrophysiological assessments in ... Read more >>

Brain (Brain : a journal of neurology)
[2020, :]

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Intrathecal B-cell activation in LGI1 antibody encephalitis.

Klaus Lehmann-Horn, Sarosh R Irani, Shengzhi Wang, Arumugam Palanichamy, Sarah Jahn, Ariele L Greenfield, Ravi Dandekar, Gildas Lepennetier, Sophia Michael, Jeffrey M Gelfand, Michael D Geschwind, Michael R Wilson, Scott S Zamvil, H-Christian von Büdingen,

OBJECTIVE:To study intrathecal B-cell activity in leucine-rich, glioma-inactivated 1 (LGI1) antibody encephalitis. In patients with LGI1 antibodies, the lack of CSF lymphocytosis or oligoclonal bands and serum-predominant LGI1 antibodies suggests a peripherally initiated immune response. However, it is unknown whether B cells within the CNS contribute to the ongoing pathogenesis ... Read more >>

Neurol Neuroimmunol Neuroinflamm (Neurology(R) neuroimmunology & neuroinflammation)
[2020, 7(2):]

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Pathologic tearfulness after limbic encephalitis: A novel disorder and its neural basis.

Georgios P D Argyropoulos, Lauren Moore, Clare Loane, Adriana Roca-Fernandez, Carmen Lage-Martinez, Oana Gurau, Sarosh R Irani, Adam Zeman, Christopher R Butler,

OBJECTIVE:We investigated the nature and neural foundations of pathologic tearfulness in a uniquely large cohort of patients who had presented with autoimmune limbic encephalitis (aLE). METHODS:We recruited 38 patients (26 men, 12 women; median age 63.06 years; interquartile range [IQR] 16.06 years) in the postacute phase of aLE who completed ... Read more >>

Neurology (Neurology)
[2020, 94(12):e1320-e1335]

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International multicenter examination of MOG antibody assays.

Markus Reindl, Kathrin Schanda, Mark Woodhall, Fiona Tea, Sudarshini Ramanathan, Jessica Sagen, James P Fryer, John Mills, Bianca Teegen, Swantje Mindorf, Nora Ritter, Ulrike Krummrei, Winfried Stöcker, Juliane Eggert, Eoin P Flanagan, Melanie Ramberger, Harald Hegen, Kevin Rostasy, Thomas Berger, Maria Isabel Leite, Jacqueline Palace, Sarosh R Irani, Russell C Dale, Christian Probst, Monika Probst, Fabienne Brilot, Sean J Pittock, Patrick Waters,

OBJECTIVE:To compare the reproducibility of 11 antibody assays for immunoglobulin (Ig) G and IgM myelin oligodendrocyte glycoprotein antibodies (MOG-IgG and MOG-IgM) from 5 international centers. METHODS:The following samples were analyzed: MOG-IgG clearly positive sera (n = 39), MOG-IgG low positive sera (n = 39), borderline negative sera (n = 13), ... Read more >>

Neurol Neuroimmunol Neuroinflamm (Neurology(R) neuroimmunology & neuroinflammation)
[2020, 7(2):]

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Refining cell-based assay to detect MOG-IgG in patients with central nervous system inflammatory diseases.

Yeseul Kim, Jae-Won Hyun, Mark R Woodhall, Yu-Mi Oh, Ji-Eun Lee, Ji Yun Jung, So Yeon Kim, Min Young Lee, Su-Hyun Kim, Woojun Kim, Sarosh R Irani, Patrick Waters, Kyungho Choi, Ho Jin Kim,

BACKGROUND:Given that the spectrum of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) associated disease is yet to be fully defined, development of sensitive and highly specific assays to identify MOG-IgG is crucial to precisely define the clinical phenotypes, disease courses and prognosis to describe the full spectrum of MOG-IgG associated diseases. ... Read more >>

Mult Scler Relat Disord (Multiple sclerosis and related disorders)
[2020, 40:101939]

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Human hippocampal CA3 damage disrupts both recent and remote episodic memories.

Thomas D Miller, Trevor T-J Chong, Anne M Aimola Davies, Michael R Johnson, Sarosh R Irani, Masud Husain, Tammy Wc Ng, Saiju Jacob, Paul Maddison, Christopher Kennard, Penny A Gowland, Clive R Rosenthal,

Neocortical-hippocampal interactions support new episodic (event) memories, but there is conflicting evidence about the dependence of remote episodic memories on the hippocampus. In line with systems consolidation and computational theories of episodic memory, evidence from model organisms suggests that the cornu ammonis 3 (CA3) hippocampal subfield supports recent, but not ... Read more >>

Elife (eLife)
[2020, 9:]

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The autoantibody-mediated encephalitides: from clinical observations to molecular pathogenesis.

Sudarshini Ramanathan, Adam Al-Diwani, Patrick Waters, Sarosh R Irani,

The autoimmune encephalitis (AE) syndromes have been characterised by the detection of autoantibodies in serum and/or cerebrospinal fluid which target the extracellular domains of specific neuroglial antigens. The clinical syndromes have phenotypes which are often highly characteristic of their associated antigen-specific autoantibody. For example, the constellation of psychiatric features and ... Read more >>

J. Neurol. (Journal of neurology)
[2019, :]

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Glycine receptor autoantibodies disrupt inhibitory neurotransmission.

Sarah J Crisp, Christine L Dixon, Leslie Jacobson, Elodie Chabrol, Sarosh R Irani, M Isabel Leite, Guy Leschziner, Sean J Slaght, Angela Vincent, Dimitri M Kullmann,

Chloride-permeable glycine receptors have an important role in fast inhibitory neurotransmission in the spinal cord and brainstem. Human immunoglobulin G (IgG) autoantibodies to glycine receptors are found in a substantial proportion of patients with progressive encephalomyelitis with rigidity and myoclonus, and less frequently in other variants of stiff person syndrome. ... Read more >>

Brain (Brain : a journal of neurology)
[2019, 142(11):3398-3410]

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Distinctive Magnetic Resonance Imaging Findings in IgLON5 Antibody Disease.

Han Chen, Jinze Wu, Sarosh R Irani,

JAMA Neurol (JAMA neurology)
[2019, :1-2]

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Hippocampal epileptogenesis in autoimmune encephalitis.

Michele Romoli, Paraskevi Krashia, Arjune Sen, Diego Franciotta, Matteo Gastaldi, Annalisa Nobili, Andrea Mancini, Elena Nardi Cesarini, Pasquale Nigro, Nicola Tambasco, Nicola B Mercuri, Lucilla Parnetti, Massimiliano Di Filippo, Marcello D'Amelio, Sarosh R Irani, Cinzia Costa, Paolo Calabresi,

OBJECTIVE:Autoantibody-mediated forms of encephalitis (AE) include neurological disorders characterized by subacute memory loss, movement disorders, and, often, frequent, focal epileptic seizures. Yet, the electrophysiological effects of these autoantibodies on neuronal function have received little attention. In this study, we assessed the effects of CSF containing autoantibodies on intrinsic and extrinsic ... Read more >>

Ann Clin Transl Neurol (Annals of clinical and translational neurology)
[2019, 6(11):2261-2269]

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Serial Anti-Myelin Oligodendrocyte Glycoprotein Antibody Analyses and Outcomes in Children With Demyelinating Syndromes.

Patrick Waters, Giulia Fadda, Mark Woodhall, Julia O'Mahony, Robert A Brown, Denise A Castro, Giulia Longoni, Sarosh R Irani, Bo Sun, E Ann Yeh, Ruth Ann Marrie, Douglas L Arnold, Brenda Banwell, Amit Bar-Or, ,

Importance:Identifying the course of demyelinating disease associated with myelin oligodendrocyte glycoprotein (MOG) autoantibodies is critical to guide appropriate treatment choices. Objective:To characterize serial anti-MOG antibody serologies and clinical and imaging features at presentation and during follow-up in an inception cohort of prospectively monitored children with acquired demyelination. Design, Setting, and ... Read more >>

JAMA Neurol (JAMA neurology)
[2019, :]

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Network-wide abnormalities explain memory variability in hippocampal amnesia.

Georgios Pd Argyropoulos, Clare Loane, Adriana Roca-Fernandez, Carmen Lage-Martinez, Oana Gurau, Sarosh R Irani, Christopher R Butler,

Patients with hippocampal amnesia play a central role in memory neuroscience but the neural underpinnings of amnesia are hotly debated. We hypothesized that focal hippocampal damage is associated with changes across the extended hippocampal system and that these, rather than hippocampal atrophy per se, would explain variability in memory between ... Read more >>

Elife (eLife)
[2019, 8:]

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Characterization of pathogenic monoclonal autoantibodies derived from muscle-specific kinase myasthenia gravis patients.

Kazushiro Takata, Panos Stathopoulos, Michelangelo Cao, Marina Mané-Damas, Miriam L Fichtner, Erik S Benotti, Leslie Jacobson, Patrick Waters, Sarosh R Irani, Pilar Martinez-Martinez, David Beeson, Mario Losen, Angela Vincent, Richard J Nowak, Kevin C O'Connor,

Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by muscle weakness and caused by pathogenic autoantibodies that bind to membrane proteins at the neuromuscular junction. Most patients have autoantibodies against the acetylcholine receptor (AChR), but a subset of patients have autoantibodies against muscle-specific tyrosine kinase (MuSK) instead. MuSK is ... Read more >>

JCI Insight (JCI insight)
[2019, 4(12):]

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Hippocampal network abnormalities explain amnesia after VGKCC-Ab related autoimmune limbic encephalitis.

Clare Loane, Georgios P D Argyropoulos, Adriana Roca-Fernández, Carmen Lage, Fintan Sheerin, Samrah Ahmed, Giovanna Zamboni, Clare Mackay, Sarosh R Irani, Christopher R Butler,

OBJECTIVE:Limbic encephalitis associated with antibodies to components of the voltage-gated potassium channel complex (VGKCC-Ab-LE) often leads to hippocampal atrophy and persistent memory impairment. Its long-term impact on regions beyond the hippocampus, and the relationship between brain damage and cognitive outcome, are poorly understood. We investigated the nature of structural and ... Read more >>

J. Neurol. Neurosurg. Psychiatry (Journal of neurology, neurosurgery, and psychiatry)
[2019, 90(9):965-974]

Cited: 1 time

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The psychopathology of NMDAR-antibody encephalitis in adults: a systematic review and phenotypic analysis of individual patient data.

Adam Al-Diwani, Adam Handel, Leigh Townsend, Thomas Pollak, M Isabel Leite, Paul J Harrison, Belinda R Lennox, David Okai, Sanjay G Manohar, Sarosh R Irani,

BACKGROUND:Early immunotherapy administration improves outcomes in patients with N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis. As most patients with NMDAR-antibody encephalitis present to psychiatrists, the psychopathology of NMDAR-antibody encephalitis needs to be clearly defined to encourage accurate clinical identification and prompt treatment. METHODS:For this systematic review, we searched PubMed for all studies published ... Read more >>

Lancet Psychiatry (The lancet. Psychiatry)
[2019, 6(3):235-246]

Cited: 3 times

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NMDA receptor antibody encephalitis presenting as Transient Epileptic Amnesia.

Sharon A Savage, Sarosh R Irani, M Isabel Leite, Adam Z Zeman,

Transient Epileptic Amnesia (TEA) is a subtype of temporal lobe epilepsy, typically presenting in a person's early 60s, and of unknown aetiology. Encephalitis caused by antibodies to NMDA receptors (NMDARE) has not previously been documented in TEA. We describe a 47-year-old male who satisfied criteria for TEA, but given his ... Read more >>

J. Neuroimmunol. (Journal of neuroimmunology)
[2019, 327:41-43]

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A multicenter comparison of MOG-IgG cell-based assays.

Patrick J Waters, Lars Komorowski, Mark Woodhall, Sabine Lederer, Masoud Majed, Jim Fryer, John Mills, Eoin P Flanagan, Sarosh R Irani, Amy C Kunchok, Andrew McKeon, Sean J Pittock,

OBJECTIVES:To compares 3 different myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG) cell-based assays (CBAs) from 3 international centers. METHODS:Serum samples from 394 patients were as follows: acute disseminated encephalomyelitis (28), seronegative neuromyelitis optica (27), optic neuritis (21 single, 2 relapsing), and longitudinally extensive (10 single, 3 recurrent). The control samples were from ... Read more >>

Neurology (Neurology)
[2019, 92(11):e1250-e1255]

Cited: 4 times

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The utility of anti-SOX2 antibodies for cancer prediction in patients with paraneoplastic neurological disorders.

Paul Maddison, Maarten J Titulaer, Jan J Verschuuren, Paul Gozzard, Bethan Lang, Sarosh R Irani, Lidia Sabater, Francesc Graus, Andrea Murray, Caroline J Chapman,

Antibodies to SOXB1 proteins in patients with paraneoplastic disorders are associated with small-cell lung cancer (SCLC), particularly in Lambert-Eaton myasthenic syndrome (LEMS). We aimed to establish if SOX2 antibodies could be used to identify SCLC and other tumours found in a range of paraneoplastic disorders and controls. SOX2 antibodies were ... Read more >>

J. Neuroimmunol. (Journal of neuroimmunology)
[2019, 326:14-18]

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The role of thymic tolerance in CNS autoimmune disease.

Adam E Handel, Sarosh R Irani, Georg A Holländer,

The contributions of the peripheral adaptive and innate immune systems to CNS autoimmunity have been extensively studied. However, the role of thymic selection in these conditions is much less well understood. The thymus is the primary lymphoid organ for the generation of T cells; thymic mechanisms ensure that cells with ... Read more >>

Nat Rev Neurol (Nature reviews. Neurology)
[2018, 14(12):723-734]

Cited: 3 times

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Association of Leucine-Rich Glioma Inactivated Protein 1, Contactin-Associated Protein 2, and Contactin 2 Antibodies With Clinical Features and Patient-Reported Pain in Acquired Neuromyotonia.

Angela Vincent, Philippa Pettingill, Rosie Pettingill, Bethan Lang, Ron Birch, Patrick Waters, Sarosh R Irani, Camilla Buckley, Osamu Watanabe, Kimiyoshi Arimura, Matthew C Kiernan,

Importance:Although acquired autoimmune neuromyotonia (NMT) is associated with voltage-gated potassium channel (VGKC)-complex antibodies, to date there has been no systematic study of autoantibodies to the specific antigens leucine-rich glioma inactivated protein 1 (LGI1), contactin-associated protein 2 (CASPR2), and contactin 2 together with the full clinical syndrome, particularly pain and autonomic ... Read more >>

JAMA Neurol (JAMA neurology)
[2018, 75(12):1519-1527]

Cited: 2 times

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Distinct HLA associations of LGI1 and CASPR2-antibody diseases.

Sophie Binks, James Varley, Wanseon Lee, Mateusz Makuch, Katherine Elliott, Jeffrey M Gelfand, Saiju Jacob, M Isabel Leite, Paul Maddison, Mian Chen, Michael D Geschwind, Eleanor Grant, Arjune Sen, Patrick Waters, Mark McCormack, Gianpiero L Cavalleri, Martin Barnardo, Julian C Knight, Sarosh R Irani,

The recent biochemical distinction between antibodies against leucine-rich, glioma-inactivated-1 (LGI1), contactin-associated protein-2 (CASPR2) and intracellular epitopes of voltage-gated potassium-channels (VGKCs) demands aetiological explanations. Given established associations between human leucocyte antigen (HLA) alleles and adverse drug reactions, and our clinical observation of frequent adverse drugs reactions in patients with LGI1 antibodies, ... Read more >>

Brain (Brain : a journal of neurology)
[2018, 141(8):2263-2271]

Cited: 4 times

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Pain and the immune system: emerging concepts of IgG-mediated autoimmune pain and immunotherapies.

Min Xu, David L H Bennett, Luis Antonio Querol, Long-Jun Wu, Sarosh R Irani, James C Watson, Sean J Pittock, Christopher J Klein,

The immune system has long been recognised important in pain regulation through inflammatory cytokine modulation of peripheral nociceptive fibres. Recently, cytokine interactions in brain and spinal cord glia as well as dorsal root ganglia satellite glia have been identified important- in pain modulation. The result of these interactions is central ... Read more >>

J. Neurol. Neurosurg. Psychiatry (Journal of neurology, neurosurgery, and psychiatry)
[2020, 91(2):177-188]

Cited: 2 times

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LGI1 expression and human brain asymmetry: insights from patients with LGI1-antibody encephalitis.

Yoonhyuk Jang, Soon-Tae Lee, Ji-Yeon Bae, Tae-Joon Kim, Jin-Sun Jun, Jangsup Moon, Keun-Hwa Jung, Kyung-Il Park, Sarosh R Irani, Kon Chu, Sang Kun Lee,

BACKGROUND:While brain asymmetry has been a fascinating issue in neuroscience, the critical mechanism remains to be elucidated. Based on some index cases with asymmetric 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) uptake in leucine-rich glioma-inactivated 1 (LGI1)-antibody encephalitis, we hypothesized LGI1 expression could be asymmetrically distributed in the human brain. METHODS:We enrolled ... Read more >>

J Neuroinflammation (Journal of neuroinflammation)
[2018, 15(1):279]

Cited: 1 time

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Hippocampal Functional Dynamics Are Clinically Implicated in Autoimmune Encephalitis With Faciobrachial Dystonic Seizures.

Julia C Nantes, Adam G Thomas, Natalie L Voets, Jonathan G Best, Clive R Rosenthal, Adam Al-Diwani, Sarosh R Irani, Charlotte J Stagg,

This is the first study to investigate functional brain activity in patients affected by autoimmune encephalitis with faciobrancial dystonic seizures (FBDS). Multimodal 3T MRI scans, including structural neuroimaging (T1-weighted, diffusion weighted) and functional neuroimaging (scene-encoding task known to activate hippocampal regions), were performed. This case series analysis included eight patients ... Read more >>

Front Neurol (Frontiers in neurology)
[2018, 9:736]

Cited: 0 times

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The clinical features, underlying immunology, and treatment of autoantibody-mediated movement disorders.

Valentina Damato, Bettina Balint, Anne-Kathrin Kienzler, Sarosh R Irani,

An increasing number of movement disorders are associated with autoantibodies. Many of these autoantibodies target the extracellular domain of neuronal surface proteins and associate with highly specific phenotypes, suggesting they have pathogenic potential. Below, we describe the phenotypes associated with some of these commoner autoantibody-mediated movement disorders, and outline increasingly ... Read more >>

Mov. Disord. (Movement disorders : official journal of the Movement Disorder Society)
[2018, 33(9):1376-1389]

Cited: 2 times

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