Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD

Cook, Lawrence J.; Rose, John; Alvey, Jessica S.; Jolley, Anna Marie; Kuhn, Renee; Marron, Brie; Pederson, Melissa; Enriquez, Rene; Yearley, Jeff; McKechnie, Stephen William; Han, May; Tomczak, Anna; Lévy, Michaël; Mealy, Maureen A.; Coleman, Jessica; Bennett, Jeffrey L.; Johnson, Ray; Barnes-Garcia, Myka; Traboulsee, Anthony; Carruthers, Robert; Lee, Lisa Eunyoung; Schubert, Julia; McMullen, Katrina; Kister, Ilya; Rimler, Zoe; Reid, Allyson; Sicotte, Nancy L.; Planchon, Sarah M.; Cohen, Jeffrey A.; Ivancic, Diane; Sedlák, J; Sand, Ilana Katz; Repovic, Pavle; Amezcua, Lilyana; Pruitt, Ana; Amundson, Erika; Chitnis, Tanuja; Mullin, Devin S.; Klawiter, Eric C.; Russo, Andrew W.; Riley, Claire; Onomichi, Kaho; Levine, Leslie; Nelson, Katherine; Nealon, Nancy; Engel, Casey; Kruse-Hoyer, Mason; Marcille, Melanie; Tornes, Leticia; Rumpf, Anne; Greer, Angela; Behne, Megan K; Rodriguez, Renee R.; Behne, Daniel W.; Blackway, Derek W.; Coords, Brian; Blaschke, Terrence F.; Sheard, Judy; Smith, Terry J.; Behne, Jacinta M.; Yeaman, Michael R.

doi:10.1212/nxi.0000000000000583

Cited by 34 publications

(36 citation statements)

References 42 publications

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“…PBMC and serum specimens from participants with NMOSD and HCs were collected and archived through the Guthy-Jackson Charitable Foundation CIRCLES study 19 or through a biorepository established at the Yale University School of Medicine, Department of Neurology. Written informed consent was obtained from all study participants before sample collection.…”

Section: Methodsmentioning

confidence: 99%

“…To this end, we acquired peripheral blood mononuclear cells (PBMCs), serum, and clinical data from the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) NMOSD biorepository. 19 We applied high-throughput technologies to assess these biospecimens using a simultaneous, hypothesis-generating strategy focused on a large set of immune cell populations, cytokines, and chemokines. Statistical methods were then used to compare cell subset frequencies and serum analyte concentrations in NMOSD vs healthy controls (HC).…”

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confidence: 99%

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High-throughput investigation of molecular and cellular biomarkers in NMOSD

Yandamuri

Jiang

Sharma

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo identify candidate biomarkers associated with neuromyelitis optica spectrum disorder (NMOSD) using high-throughput technologies that broadly assay the concentrations of serum analytes and frequencies of immune cell subsets.MethodsSera, peripheral blood mononuclear cells (PBMCs), and matched clinical data from participants with NMOSD and healthy controls (HCs) were obtained from the Collaborative International Research in Clinical and Longitudinal Experience Study NMOSD biorepository. Flow cytometry panels were used to measure the frequencies of 39 T-cell, B-cell, regulatory T-cell, monocyte, natural killer (NK) cell, and dendritic cell subsets in unstimulated PBMCs. In parallel, multiplex proteomics assays were used to measure 46 serum cytokines and chemokines in 2 independent NMOSD and HC cohorts. Multivariable regression models were used to assess molecular and cellular profiles in NMOSD compared with HC.ResultsNMOSD samples had a lower frequency of CD16+CD56+ NK cells. Both serum cohorts and multivariable logistic regression revealed increased levels of B-cell activating factor associated with NMOSD. Interleukin 6, CCL22, and CCL3 were also elevated in 1 NMOSD cohort of the 2 analyzed. Multivariable linear regression of serum analyte levels revealed a correlation between CX3CL1 (fractalkine) levels and the number of days since most recent disease relapse.ConclusionsIntegrative analyses of cytokines, chemokines, and immune cells in participants with NMOSD and HCs provide congruence with previously identified biomarkers of NMOSD and highlight CD16+CD56+ NK cells and CX3CL1 as potential novel biomarker candidates.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

High-throughput investigation of molecular and cellular biomarkers in NMOSD

Yandamuri

Jiang

Sharma

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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“…Neuromyelitis optica spectrum disorders (NMOSDs) are rare and, in most cases, relapsing inflammatory diseases of the central nervous system (CNS) ( 10 ). In the majority of cases, NMOSDs are associated with serum immunoglobulin G (IgG) autoantibodies (Abs) targeting the astrocyte aquaporin-4 (AQP4) water channel ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Pain in NMOSD and MOGAD: A Systematic Literature Review of Pathophysiology, Symptoms, and Current Treatment Strategies

2020

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Neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) are autoimmune inflammatory disorders of the central nervous system (CNS). Pain is highly prevalent and debilitating in NMOSD and MOGAD with a severe impact on quality of life, and there is a critical need for further studies to successfully treat and manage pain in these rare disorders. In NMOSD, pain has a prevalence of over 80%, and pain syndromes include neuropathic, nociceptive, and mixed pain, which can emerge in acute relapse or become chronic during the disease course. The impact of pain in MOGAD has only recently received increased attention, with an estimated prevalence of over 70%. These patients typically experience not only severe headache, retrobulbar pain, and/or pain on eye movement in optic neuritis but also neuropathic and nociceptive pain. Given the high relevance of pain in MOGAD and NMOSD, this article provides a systematic review of the current literature pertaining to pain in both disorders, focusing on the etiology of their respective pain syndromes and their pathophysiological background. Acknowledging the challenge and complexity of diagnosing pain, we also provide a mechanism-based classification of NMOSD- and MOGAD-related pain syndromes and summarize current treatment strategies.

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“…Neuromyelitis optica spectrum disorders (NMOSD) are inflammatory diseases of the central nervous system defined by a clinical spectrum of optic neuritis (ON), myelitis, and more rarely, brainstem and cerebral attacks ( Wingerchuk et al , 2015 ). The majority of patients (about 70%) are seropositive for immunoglobulin (Ig)G antibodies against the astrocytic water channel aquaporin-4 (AQP4-IgG+) ( Mori et al , 2018 ; Cook et al , 2019 ). Magnetic resonance imaging (MRI) identification of T2-hyperintense brain lesions is useful for initial differential diagnosis and during acute attacks, but brain lesions are often non-specific for disability or prognosis in NMOSD ( Kremer et al , 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Imaging markers of disability in aquaporin-4 immunoglobulin G seropositive neuromyelitis optica: a graph theory study

Chien

Oertel

Siebert

et al. 2019

Brain Communications

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Neuromyelitis optica spectrum disorders lack imaging biomarkers associated with disease course and supporting prognosis. This complex and heterogeneous set of disorders affects many regions of the central nervous system, including the spinal cord and visual pathway. Here, we use graph theory-based multimodal network analysis to investigate hypothesis-free mixed networks and associations between clinical disease with neuroimaging markers in 40 aquaporin-4-immunoglobulin G antibody seropositive patients (age = 48.16 ± 14.3 years, female:male = 36:4) and 31 healthy controls (age = 45.92 ± 13.3 years, female:male = 24:7). Magnetic resonance imaging measures included total brain and deep grey matter volumes, cortical thickness and spinal cord atrophy. Optical coherence tomography measures of the retina and clinical measures comprised of clinical attack types and expanded disability status scale were also utilized. For multimodal network analysis, all measures were introduced as nodes and tested for directed connectivity from clinical attack types and disease duration to systematic imaging and clinical disability measures. Analysis of variance, with group interactions, gave weights and significance for each nodal association (hyperedges). Connectivity matrices from 80% and 95% F-distribution networks were analyzed and revealed the number of combined attack types and disease duration as the most connected nodes, directly affecting changes in several regions of the central nervous system. Subsequent multivariable regression models, including interaction effects with clinical parameters, identified associations between decreased nucleus accumbens (β = −0.85, P = 0.021) and caudate nucleus (β = −0.61, P = 0.011) volumes with higher combined attack type count and longer disease duration, respectively. We also confirmed previously reported associations between spinal cord atrophy with increased number of clinical myelitis attacks. Age was the most important factor associated with normalized brain volume, pallidum volume, cortical thickness and the expanded disability status scale score. The identified imaging biomarker candidates warrant further investigation in larger-scale studies. Graph theory-based multimodal networks allow for connectivity and interaction analysis, where this method may be applied in other complex heterogeneous disease investigations with different outcome measures.

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Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD

Cited by 34 publications

References 42 publications

High-throughput investigation of molecular and cellular biomarkers in NMOSD

High-throughput investigation of molecular and cellular biomarkers in NMOSD

Pain in NMOSD and MOGAD: A Systematic Literature Review of Pathophysiology, Symptoms, and Current Treatment Strategies

Imaging markers of disability in aquaporin-4 immunoglobulin G seropositive neuromyelitis optica: a graph theory study

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