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Schirmer, L.* ; Srivastava, R.* ; Kalluri, S.R.* ; Boettinger, S.* ; Herwerth, M.* ; Carassiti, D.* ; Srivastava, B. ; Gempt, J.* ; Schlegel, J.* ; Kuhlmann, T.* ; Korn, T.* ; Reynolds, R.* ; Hemmer, B.*

Differential loss of KIR4.1 immunoreactivity in multiple sclerosis lesions.

Ann. Neurol. 75, 810-828 (2014)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Objective: Serum antibodies against the glial potassium channel KIR4.1 are found in a subpopulation of multiple sclerosis (MS) patients. Little is known about the expression of KIR4.1 in human normal brain tissue and in MS lesions. Methods: We analyzed the expression pattern of KIR4.1 in normal brain tissue and MS lesions of the subcortical white matter by immunohistochemistry. Markers of related glial proteins, myelin, and inflammatory cells were analyzed in parallel. Results: KIR4.1 is expressed in oligodendrocytes and astrocytes in the adult human brain. In oligodendrocytes, KIR4.1 appears as a homotetramer channel, in astrocytes as homo- and heterotetramer channels together with KIR5.1. In acute MS lesions, KIR4.1 immunoreactivity (IR) was differentially lost on periplaque oligodendrocytes and perivascular astrocytes. In part of acute lesions, complement activation, apoptotic KIR4.1(+) glial cells, and phagocytes containing KIR4.1(+) fragments accompanied loss of glial KIR4.1 IR. Periplaque reactive astrocytes showed enhanced IR for both KIR4.1 and KIR5.1. In chronic active MS lesions, apart from a general loss of oligodendrocytes in the demyelinated area, we observed a decrease of astroglial KIR4.1 but not glial fibrillary acidic protein IR. In chronic inactive and remyelinating MS lesions, KIR4.1 IR was restored on astrocytes and found in a subset of presumably new myelinating oligodendrocytes. Interpretation: The expression profile of KIR4.1 in glial cells and stage-dependent alterations of KIR4.1 IR in MS lesions are compatible with an immune response against KIR4.1 at least in a subset of MS patients.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Rectifying K+ Channel; Neuromyelitis-optica; Spinal-cord; White-matter; In-vivo; Potassium Channels; Gap-junctions; Glial-cells; Knock-out; B-cells
Sprache englisch
Veröffentlichungsjahr 2014
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 0364-5134
e-ISSN 1531-8249
Zeitschrift Annals of Neurology
Quellenangaben Band: 75, Heft: 6, Seiten: 810-828 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Hoboken
Begutachtungsstatus Peer reviewed
POF Topic(s) 30503 - Chronic Diseases of the Lung and Allergies
Forschungsfeld(er) Lung Research
PSP-Element(e) G-551800-001
Erfassungsdatum 2014-08-11