{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:08:02Z","timestamp":1792098482739,"version":"4.4.0"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,8,21]],"date-time":"2009-08-21T00:00:00Z","timestamp":1250812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Severe inflammation and astrocyte loss with profound demyelination in spinal cord and optic nerves are typical pathological features of neuromyelitis optica (NMO). A diagnostic hallmark of this disease is the presence of serum autoantibodies against the water channel aquaporin\u20104 (AQP\u20104) on astrocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We induced acute T\u2010cell\u2013mediated experimental autoimmune encephalomyelitis in Lewis rats and confronted the animals with an additional application of immunoglobulins from AQP\u20104 antibody\u2013positive and \u2013negative NMO patients, multiple sclerosis patients, and control subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The immunoglobulins from AQP\u20104 antibody\u2013positive NMO patients are pathogenic. When they reach serum titers in experimental animals comparable with those seen in NMO patients, they augment clinical disease and induce lesions in the central nervous system that are similar in structure and distribution to those seen in NMO patients, consisting of AQP\u20104 and astrocyte loss, granulocytic infiltrates, T cells and activated macrophages\/microglia cells, and an extensive immunoglobulin and complement deposition on astrocyte processes of the perivascular and superficial glia limitans. AQP\u20104 antibody containing NMO immunoglobulin injected into na\u00efve rats, young rats with leaky blood\u2013brain barrier, or after transfer of a nonencephalitogenic T\u2010cell line did not induce disease or neuropathological alterations in the central nervous system. Absorption of NMO immunoglobulins with AQP\u20104\u2013transfected cells, but not with mock\u2010transfected control cells, reduced the AQP\u20104 antibody titers and was associated with a reduction of astrocyte pathology after transfer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Human anti\u2013AQP\u20104 antibodies are not only important in the diagnosis of NMO but also augment disease and induce NMO\u2010like lesions in animals with T\u2010cell\u2013mediated brain inflammation. Ann Neurol 2009;66:630\u2013643<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.21837","type":"journal-article","created":{"date-parts":[[2009,8,21]],"date-time":"2009-08-21T11:13:05Z","timestamp":1250853185000},"page":"630-643","source":"Crossref","is-referenced-by-count":507,"title":["Neuromyelitis optica: Pathogenicity of patient immunoglobulin in 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