• Annals of neurology · Jun 2014

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

    • Lucas Schirmer, Rajneesh Srivastava, Sudhakar Reddy Kalluri, Susanne Böttinger, Marina Herwerth, Daniele Carassiti, Barkha Srivastava, Jens Gempt, Jürgen Schlegel, Tanja Kuhlmann, Thomas Korn, Richard Reynolds, and Bernhard Hemmer.
    • Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
    • Ann. Neurol. 2014 Jun 1; 75 (6): 810-28.

    ObjectiveSerum 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.MethodsWe 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.ResultsKIR4.1 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.InterpretationThe 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.© 2014 American Neurological Association.

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