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Differential loss of KIR4.1 immunoreactivity in multiple sclerosis lesions
Author(s) -
Schirmer Lucas,
Srivastava Rajneesh,
Kalluri Sudhakar Reddy,
Böttinger Susanne,
Herwerth Marina,
Carassiti Daniele,
Srivastava Barkha,
Gempt Jens,
Schlegel Jürgen,
Kuhlmann Tanja,
Korn Thomas,
Reynolds Richard,
Hemmer Bernhard
Publication year - 2014
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24168
Subject(s) - multiple sclerosis , differential (mechanical device) , differential diagnosis , medicine , pathology , physics , immunology , thermodynamics
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. Ann Neurol 2014;75:810–828