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


CONCLUSIONS
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.
Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Lucas
L
Schirmer
Rajneesh
R
Srivastava
Sudhakar Reddy
SR
Kalluri
Susanne
S
Böttinger
Marina
M
Herwerth
Daniele
D
Carassiti
Barkha
B
Srivastava
Jens
J
Gempt
Jürgen
J
Schlegel
Tanja
T
Kuhlmann
Thomas
T
Korn
Richard
R
Reynolds
Bernhard
B
Hemmer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D051401:Aquaporin 4 / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D016923:Cell Death / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid; D056784:Leukoencephalopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000150:complications / Q000473:pathology*; D009185:Myelin Proteins / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism / Q000473:pathology; D024661:Potassium Channels, Inwardly Rectifying / Q000276:immunology / Q000378:metabolism*; D000098854:Kcnj10 Channel; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D051401:Aquaporin 4; D007074:Immunoglobulin G; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D024661:Potassium Channels, Inwardly Rectifying; D000098854:Kcnj10 Channel; C496030:AQP4 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule