Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.

<h4>Background</h4>Multiple sclerosis (MS) and neuromyelitis optica (NMO) occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx) pathology and disease aggressiv...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Katsuhisa Masaki, Satoshi O Suzuki, Takuya Matsushita, Takeshi Matsuoka, Shihoko Imamura, Ryo Yamasaki, Makiko Suzuki, Toshihiko Suenaga, Toru Iwaki, Jun-Ichi Kira
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2013
Materias:
R
Q
Acceso en línea:https://doaj.org/article/23d902ac90ca4ff084b8d8f5515524ec
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:23d902ac90ca4ff084b8d8f5515524ec
record_format dspace
spelling oai:doaj.org-article:23d902ac90ca4ff084b8d8f5515524ec2021-11-18T08:58:25ZConnexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.1932-620310.1371/journal.pone.0072919https://doaj.org/article/23d902ac90ca4ff084b8d8f5515524ec2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23991165/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Multiple sclerosis (MS) and neuromyelitis optica (NMO) occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx) pathology and disease aggressiveness in Asian patients with MS and NMO.<h4>Methods/principal findings</h4>Samples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD), six with MS, and 20 with other neurological diseases (OND). Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59), chronic active (n=58) and chronic inactive (n=23). Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090). Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296). Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients.<h4>Conclusions</h4>These findings suggest that autoantibody-independent astrocytic Cx43 loss may relate to disease aggressiveness and distal oligodendrogliopathy in both MS and NMO.Katsuhisa MasakiSatoshi O SuzukiTakuya MatsushitaTakeshi MatsuokaShihoko ImamuraRyo YamasakiMakiko SuzukiToshihiko SuenagaToru IwakiJun-Ichi KiraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e72919 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Katsuhisa Masaki
Satoshi O Suzuki
Takuya Matsushita
Takeshi Matsuoka
Shihoko Imamura
Ryo Yamasaki
Makiko Suzuki
Toshihiko Suenaga
Toru Iwaki
Jun-Ichi Kira
Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.
description <h4>Background</h4>Multiple sclerosis (MS) and neuromyelitis optica (NMO) occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx) pathology and disease aggressiveness in Asian patients with MS and NMO.<h4>Methods/principal findings</h4>Samples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD), six with MS, and 20 with other neurological diseases (OND). Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59), chronic active (n=58) and chronic inactive (n=23). Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090). Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296). Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients.<h4>Conclusions</h4>These findings suggest that autoantibody-independent astrocytic Cx43 loss may relate to disease aggressiveness and distal oligodendrogliopathy in both MS and NMO.
format article
author Katsuhisa Masaki
Satoshi O Suzuki
Takuya Matsushita
Takeshi Matsuoka
Shihoko Imamura
Ryo Yamasaki
Makiko Suzuki
Toshihiko Suenaga
Toru Iwaki
Jun-Ichi Kira
author_facet Katsuhisa Masaki
Satoshi O Suzuki
Takuya Matsushita
Takeshi Matsuoka
Shihoko Imamura
Ryo Yamasaki
Makiko Suzuki
Toshihiko Suenaga
Toru Iwaki
Jun-Ichi Kira
author_sort Katsuhisa Masaki
title Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.
title_short Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.
title_full Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.
title_fullStr Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.
title_full_unstemmed Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.
title_sort connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/23d902ac90ca4ff084b8d8f5515524ec
work_keys_str_mv AT katsuhisamasaki connexin43astrocytopathylinkedtorapidlyprogressivemultiplesclerosisandneuromyelitisoptica
AT satoshiosuzuki connexin43astrocytopathylinkedtorapidlyprogressivemultiplesclerosisandneuromyelitisoptica
AT takuyamatsushita connexin43astrocytopathylinkedtorapidlyprogressivemultiplesclerosisandneuromyelitisoptica
AT takeshimatsuoka connexin43astrocytopathylinkedtorapidlyprogressivemultiplesclerosisandneuromyelitisoptica
AT shihokoimamura connexin43astrocytopathylinkedtorapidlyprogressivemultiplesclerosisandneuromyelitisoptica
AT ryoyamasaki connexin43astrocytopathylinkedtorapidlyprogressivemultiplesclerosisandneuromyelitisoptica
AT makikosuzuki connexin43astrocytopathylinkedtorapidlyprogressivemultiplesclerosisandneuromyelitisoptica
AT toshihikosuenaga connexin43astrocytopathylinkedtorapidlyprogressivemultiplesclerosisandneuromyelitisoptica
AT toruiwaki connexin43astrocytopathylinkedtorapidlyprogressivemultiplesclerosisandneuromyelitisoptica
AT junichikira connexin43astrocytopathylinkedtorapidlyprogressivemultiplesclerosisandneuromyelitisoptica
_version_ 1718421069305479168