TY - JOUR
T1 - Differential loss of KIR4.1 immunoreactivity in multiple sclerosis lesions
AU - Schirmer, Lucas
AU - Srivastava, Rajneesh
AU - Kalluri, Sudhakar Reddy
AU - Böttinger, Susanne
AU - Herwerth, Marina
AU - Carassiti, Daniele
AU - Srivastava, Barkha
AU - Gempt, Jens
AU - Schlegel, Jürgen
AU - Kuhlmann, Tanja
AU - Korn, Thomas
AU - Reynolds, Richard
AU - Hemmer, Bernhard
PY - 2014/6
Y1 - 2014/6
N2 - 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
AB - 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
UR - http://www.scopus.com/inward/record.url?scp=84903731417&partnerID=8YFLogxK
U2 - 10.1002/ana.24168
DO - 10.1002/ana.24168
M3 - Article
C2 - 24777949
AN - SCOPUS:84903731417
SN - 0364-5134
VL - 75
SP - 810
EP - 828
JO - Annals of Neurology
JF - Annals of Neurology
IS - 6
ER -