2018
DOI: 10.1007/s00401-018-1950-8
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Circulating AQP4-specific auto-antibodies alone can induce neuromyelitis optica spectrum disorder in the rat

Abstract: It is well established that the binding of pathogenic aquaporin-4 (AQP4)-specific autoantibodies to astrocytes may initiate a cascade of events culminating in the destruction of these cells and in the formation of large tissue-destructive lesions typical for patients with neuromyelitis optica spectrum disorders (NMOSD). To date, not a single experimental study has shown that the systemic presence of the antibody alone can induce any damage to the central nervous system (CNS), while pathological studies on brai… Show more

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Cited by 67 publications
(57 citation statements)
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“…The classical examples of human diseases are neuromyelitis optica spectrum disorders with antibodies against the astrocytic water channel aquaporin 4 (Lennon, Kryzer, Pittock, Verkman, & Hinson, ) and the inflammatory demyelinating disease associated with specific demyelinating autoantibodies against myelin oligodendrocyte glycoprotein (Hennes, Baumann, Lechner, & Rostasy, ). For both diseases, excellent experimental models are available, including MOG induced experimental autoimmune encephalomyelitis in rats, guinea pigs, and marmoset monkeys (Lassmann & Bradl, ; Linington et al, ) and passive transfer models using aquaporin 4 specific T‐cells together with human or animal derived pathogenic autoantibodies against aquaporin 4 (Bradl et al, ; Hillebrand et al, ). The reaction of glia in these models not only depends upon the mechanisms of inflammation but also on the extent and type of antibody mediated tissue injury.…”
Section: The Spectrum Of Inflammatory Diseases Of the Brain And Spinamentioning
confidence: 99%
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“…The classical examples of human diseases are neuromyelitis optica spectrum disorders with antibodies against the astrocytic water channel aquaporin 4 (Lennon, Kryzer, Pittock, Verkman, & Hinson, ) and the inflammatory demyelinating disease associated with specific demyelinating autoantibodies against myelin oligodendrocyte glycoprotein (Hennes, Baumann, Lechner, & Rostasy, ). For both diseases, excellent experimental models are available, including MOG induced experimental autoimmune encephalomyelitis in rats, guinea pigs, and marmoset monkeys (Lassmann & Bradl, ; Linington et al, ) and passive transfer models using aquaporin 4 specific T‐cells together with human or animal derived pathogenic autoantibodies against aquaporin 4 (Bradl et al, ; Hillebrand et al, ). The reaction of glia in these models not only depends upon the mechanisms of inflammation but also on the extent and type of antibody mediated tissue injury.…”
Section: The Spectrum Of Inflammatory Diseases Of the Brain And Spinamentioning
confidence: 99%
“…Another type of brain and spinal cord inflammation involves the cooperation of T-cells (most likely CD4 + cells) and specific pathogenic autoantibodies (Pohl et al, 2013 (Lassmann & Bradl, 2017;Linington et al, 1988) and passive transfer models using aquaporin 4 specific T-cells together with human or animal derived pathogenic autoantibodies against aquaporin 4 (Bradl et al, 2009;Hillebrand et al, 2019). The reaction of glia in these models not only depends upon the mechanisms of inflammation but also on the extent and type of antibody mediated tissue injury.…”
Section: The Spectrum Of Inflammatory Diseases Of the Brain And Spimentioning
confidence: 99%
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“…However, such titers are frequently seen in NMOSD [69], where "low titer patients experience the same disease course as medium-titer and high-titer anti-AQP4 antibody patients" [70]. Low titers of AQP4-reactive antibodies could indicate their depletion from the circulation, for example by their binding to AQP4 expressing cells in the CNS [71] or in peripheral organs [72,73]. However, we did not see any astrocyte-destructive, antibodyconsuming lesions in the CNS (data not shown), had no evidence for AQP4 loss resulting from antibody binding to astrocytes in the area postrema (supplementary information S8), and could not detect AQP4 loss in kidney collecting duct epithelial cells which otherwise show most robust responses to AQP4-reactive antibodies [73] (data not shown).…”
Section: Discussionmentioning
confidence: 99%
“…Low titers of AQP4-reactive antibodies could indicate their depletion from the circulation, for example by their binding to AQP4 expressing cells in the CNS [71] or in peripheral organs [72,73]. However, we did not see any astrocyte-destructive, antibodyconsuming lesions in the CNS (data not shown), had no evidence for AQP4 loss resulting from antibody binding to astrocytes in the area postrema (supplementary information S8), and could not detect AQP4 loss in kidney collecting duct epithelial cells which otherwise show most robust responses to AQP4-reactive antibodies [73] (data not shown). Hence, these AQP4-antibody seropositive Lewis rats might resemble human patients which can become AQP4-antibody positive months and decades prior to the onset of clinical NMOSD [74,75].…”
Section: Discussionmentioning
confidence: 99%