Neuromyelitis optica study model based on chronic infusion of autoantibodies in rat cerebrospinal fluid

Marignier, Romain; Ruiz, Anne; Cavagna, Sylvie; Nicole, Annie; Watrin, Chantal; Touret, Monique; Parrot, Sandrine; Malleret, Gaël; Peyron, Christelle; Benetollo, Claire; Auvergnon, Nathalie; Vukusic, Sandra; Giraudon, Pascale

doi:10.1186/s12974-016-0577-8

Cited by 47 publications

(58 citation statements)

References 53 publications

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“…One study[19] was not included due to lack of normal controls (S1 Fig). Compared with studies in healthy controls, three studies in MS patients showed an association of positivity of anti-KIR4.1[10,11,14] and seven studies, including our own, showed no significant differences[12,13,16,20,21,27–29] (Fig 4). The statistical heterogeneity between studies was over 75% and did not allow data pooling to perform meta-analysis.…”

Section: Resultscontrasting

confidence: 45%

“…The studies were developed in the USA (3)[15,16,20], Germany (2)[10,11], France (2)[12,27], Japan (2)[28,29], Israel (1)[14], Italy (1)[21], Spain (1), Switzerland (1)[19], and Turkey (1)[13]. They showed substantial variability in the technical determination of anti-KIR4.1 and control group populations.…”

Section: Resultsmentioning

confidence: 99%

“…They showed substantial variability in the technical determination of anti-KIR4.1 and control group populations. The methodological quality was qualified as week in five studies[13,21,27–29], moderate in four studies[11,16,20,30] plus our own, and strong in three studies[10,14,15]. One study[19] was not included due to lack of normal controls (S1 Fig).…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, these studies did not identify clinical, radiological or therapeutic features that were specifically associated with the presence of anti-KIR4.1 antibodies in MS patients. The results from early replication studies using the KIR4.1 extracellular loop (residues 83–120) peptide to test anti-KIR4.1 antibodies by ELISA were insufficiently consistent to demonstrate a clear association of anti-KIR4.1 and MS even though the same detection assay was used[12,27]. A thorough replication study including a multimodal approach also failed to confirm the association of anti-KIR4.1 antibodies with MS[16].…”

Section: Discussionmentioning

confidence: 99%

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Absence of antibodies against KIR4.1 in multiple sclerosis: A three-technique approach and systematic review

et al. 2017

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IntroductionAntibodies targeting the inward-rectifying potassium channel KIR4.1 have been associated with multiple sclerosis (MS) but studies using diverse techniques have failed to replicate this association. The detection of these antibodies is challenging; KIR4.1 glycosylation patterns and the use of diverse technical approaches may account for the disparity of results. We aimed to replicate the association using three different approaches to overcome the technical limitations of a single technique. We also performed a systematic review to examine the association of anti-KIR4.1 antibodies with MS.MethodsSerum samples from patients with MS (n = 108) and controls (n = 77) were tested for the presence of anti-KIR4.1 antibodies using three methods: 1) by ELISA with the low-glycosylated fraction of recombinant KIR4.1 purified from transfected HEK293 cells according to original protocols; 2) by immunocytochemistry using KIR4.1-transfected HEK293 cells; and 3) by immunocytochemistry using the KIR4.1.-transfected MO3.13 oligodendrocyte cell line. We developed a systematic review and meta-analysis of the association of anti-KIR4.1 antibodies with MS according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsWe did not detect anti-KIR4.1 antibodies in the MS patients or in controls using ELISA. Neither did we detect any significant reactivity against the antigen on the cell surface using the KIR4.1-transfected HEK293 cells or the KIR4.1-transfected MO3.13 cells. We included 13 prospective controlled studies in the systematic review. Only three studies showed a positive association between anti-KIR4.1 and MS. Clinical and statistical heterogeneity between studies precluded meta-analysis of their results.ConclusionWe found no association between anti-KIR4.1 antibody positivity and MS. Although this lack of replication may be due to technical limitations, evidence from our study and others is mounting against the role of KIR4.1 as a relevant MS autoantigen.

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Section: Resultscontrasting

confidence: 45%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Absence of antibodies against KIR4.1 in multiple sclerosis: A three-technique approach and systematic review

et al. 2017

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“…Curiously, similar pathology was seen in rats pre‐treated with cobra venom factor, suggesting a complement‐independent mechanism. A related model involved continuous intraventricular infusion of patient‐derived AQP4‐IgG for 7 days by osmotic mini‐pump . Human IgG was seen in brain, spinal cord and optic nerve, with the loss of AQP4 and reactive astrocytes in spinal cord and optic nerve, and demyelination and axonal injury in spinal cord.…”

Section: Passive Transfer Models Of Nmomentioning

confidence: 99%

Experimental animal models of aquaporin‐4‐IgG‐seropositive neuromyelitis optica spectrum disorders: progress and shortcomings

Duan

2019

Brain Pathology

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Neuromyelitis optica spectrum disorders (NMOSD) is a heterogeneous group of neuroinflammatory conditions associated with demyelination primarily in spinal cord and optic nerve, and to a lesser extent in brain. Most NMOSD patients are seropositive for IgG autoantibodies against aquaporin-4 (AQP4-IgG), the principal water channel in astrocytes. There has been interest in establishing experimental animal models of seropositive NMOSD (herein referred to as NMO) in order to elucidate NMO pathogenesis mechanisms and to evaluate drug candidates. An important outcome of early NMO animal models was evidence for a pathogenic role of AQP4-IgG. However, available animal models of NMO, based largely on passive transfer to rodents of AQP4-IgG or transfer of AQP4-sensitized T cells, often together with pro-inflammatory maneuvers, only partially recapitulate the clinical and pathological features of human NMO, and are inherently biased toward humoral or cellular immune mechanisms. This review summarizes current progress and shortcomings in experimental animal models of seropositive NMOSD, and opines on the import of advancing animal models.

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In Vivo Determination of Glutamate Uptake by Brain Microdialysis

2017

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Neuromyelitis optica study model based on chronic infusion of autoantibodies in rat cerebrospinal fluid

Cited by 47 publications

References 53 publications

Absence of antibodies against KIR4.1 in multiple sclerosis: A three-technique approach and systematic review

Absence of antibodies against KIR4.1 in multiple sclerosis: A three-technique approach and systematic review

Experimental animal models of aquaporin‐4‐IgG‐seropositive neuromyelitis optica spectrum disorders: progress and shortcomings

In Vivo Determination of Glutamate Uptake by Brain Microdialysis

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