Neuromyelitis optica in patients with increased interferon alpha concentrations

Williams, J. Raymond; McGlasson, Sarah; Irani, Sarosh R.; Duffy, Darragh; Crow, Yanick J.; Hunt, David

doi:10.1016/s1474-4422(19)30445-4

Cited by 14 publications

(13 citation statements)

References 13 publications

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“…Finally, plasma IFNα levels were investigated as IFNα is associated with SLE, the development of neurological autoantibody‐mediated complications in SLE, and is directly a neurotoxic cytokine 15–17 . Plasma IFNα levels were ~100‐fold higher in patients with SLE compared with HCs/DCs (both p < 0.0001; Fig 3A), with fewer striking differences in CSF (Fig 3B).…”

Section: Resultsmentioning

confidence: 99%

“…Controls, but Not from NPSLE Finally, plasma IFNα levels were investigated as IFNα is associated with SLE, the development of neurological autoantibody-mediated complications in SLE, and is directly a neurotoxic cytokine. [15][16][17] Plasma IFNα levels were 100-fold higher in patients with SLE compared , an isotype control (B1), and plasma from disease controls (n = 68), healthy controls (n = 36), and patients with SLE (n = 35), including those with active neuropsychiatric systemic lupus erythematosus (NPSLE). Significant differences (Kruskal Wallis test with post hoc Dunn's correction) were observed between patients with SLE and healthy controls (p = 0.03*) and disease controls (p = 0.009**), but not between active NPSLE and other cases of SLE (ns).…”

Section: Ifnα Levels Better Distinguish Sle Frommentioning

confidence: 99%

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Absence of Neuronal Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus

Varley

Andersson

Grant

et al. 2020

Annals of Neurology

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This study aimed to characterise both neuronal autoantibodies and levels of interferon α, two proposed causative agents in neuropsychiatric systemic lupus erythematosus (NPSLE). Cerebrospinal fluid (CSF) and plasma from 35 patients with systemic lupus erythematosus (SLE; 15 with NPSLE) showed no antibodies against natively expressed N‐methyl‐D‐aspartate receptors (NMDARs), or the surface of live hippocampal neurons. By comparison to controls (n = 104), patients with SLE had antibodies that bound to a peptide representing the extracellular domain of NMDARs (p < 0.0001), however, binding was retained against both rearranged peptides and no peptide (r = 0.85 and r = 0.79, respectively, p < 0.0001). In summary, neuronal‐surface reactive antibodies were not detected in NPSLE. Further, while interferon α levels were higher in SLE (p < 0.0001), they lacked specificity for NPSLE. Our findings mandate a search for novel biomarkers in this condition. ANN NEUROL 2020;88:1244–1250

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Section: Resultsmentioning

confidence: 99%

Section: Ifnα Levels Better Distinguish Sle Frommentioning

confidence: 99%

Absence of Neuronal Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus

Varley

Andersson

Grant

et al. 2020

Annals of Neurology

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“…Moreover, we have shown that similarly to brain pathology (17), lesion formation in the optic nerve was dependent on type I IFN signaling, pathology being completely absent in mice lacking the receptor for type I IFN. Furthermore, clinical studies have shown an association between elevated levels of serum type I IFN (IFN-alpha) and development and activity of NMOSD (33,34) as well as negative effect of IFN-β in NMOSD patients (35)(36)(37)(38)(39). Our recent study showed that microglia are the main responders to type I IFN in NMOSDlike pathology and that they are critical for the development of the disease (16).…”

Section: Discussionmentioning

confidence: 96%

An Experimental Model of Neuromyelitis Optica Spectrum Disorder–Optic Neuritis: Insights Into Disease Mechanisms

et al. 2021

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Background: Optic neuritis (ON) is a common inflammatory optic neuropathy, which often occurs in neuromyelitis optica spectrum disease (NMOSD). An experimental model of NMOSD-ON may provide insight into disease mechanisms.Objective: To examine the pathogenicity of autoantibodies targeting the astrocyte water channel aquaporin-4 [aquaporin-4 (AQP4)-immunoglobulin G (AQP4-IgG)] in the optic nerve.Materials and Methods: Purified IgG from an AQP4-IgG-positive NMOSD-ON patient was together with human complement (C) given to wild-type (WT) and type I interferon (IFN) receptor-deficient mice (IFNAR1-KO) as two consecutive intrathecal injections into cerebrospinal fluid via cisterna magna. The optic nerves were isolated, embedded in paraffin, cut for histological examination, and scored semi-quantitatively in a blinded fashion. In addition, optic nerves were processed to determine selected gene expression by quantitative real-time PCR.Results: Intrathecal injection of AQP4-IgG+C induced astrocyte pathology in the optic nerve with loss of staining for AQP4 and glial fibrillary acidic protein (GFAP), deposition of C, and demyelination, as well as upregulation of gene expression for interferon regulatory factor-7 (IRF7) and CXCL10. Such pathology was not seen in IFNAR1-KO mice nor in control mice.Conclusion: We describe induction of ON in an animal model for NMOSD and show a requirement for type I IFN signaling in the disease process.

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“…Meanwhile, growing evidence indicates that the elevation of serum IFN-α level might also take part in the pathogenesis or disease activity of anti-AQP4-positive NMO (9-11). There are cases of NMO induced by the therapeutic use of recombinant IFN-α for other diseases (10,11). Moreover, there was a case of anti-AQP4-positive NMO in a child with increased endogenous IFN-α level (12).…”

Section: Discussionmentioning

confidence: 99%

Fulminant Course of Neuromyelitis Optica in a Patient With Anti-MDA5 Antibody-Positive Dermatomyositis: A Case Report

et al. 2020

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Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody is a myositis-specific marker detected in clinically amyopathic dermatomyositis (DM). DM with anti-MDA5 antibody can be accompanied by rapidly progressive interstitial lung disease (RP-ILD) and other autoimmune disorders. Until now, only one case of neuromyelitis optica (NMO) with anti-MDA5-positive DM has been reported worldwide, in which the patient achieved a favorable outcome with intensive immunotherapy. We report a case of NMO in a patient with anti-MDA5-positive DM complicated by ILD and rheumatoid arthritis. Our patient experienced a fulminant course of NMO, rather than RP-ILD, in the presence of hyperferritinemia, which resulted in profound neurological sequelae despite immunotherapy including rituximab.

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Neuromyelitis optica in patients with increased interferon alpha concentrations

Cited by 14 publications

References 13 publications

Absence of Neuronal Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus

Absence of Neuronal Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus

An Experimental Model of Neuromyelitis Optica Spectrum Disorder–Optic Neuritis: Insights Into Disease Mechanisms

Fulminant Course of Neuromyelitis Optica in a Patient With Anti-MDA5 Antibody-Positive Dermatomyositis: A Case Report

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