Abstract | BACKGROUND:
Inflammation in neuromyelitis optica (NMO) is triggered by a serum antibody against the aquaporin-4 (AQP4). This process requires antibody penetration of the blood-brain barrier (BBB), but the mechanisms for BBB disruption in NMO remain unknown. OBJECTIVE: METHODS: RESULTS: NMO patients exhibited significantly elevated MMP-2, TIMP-1, interleukin-6, and MMP-2/TIMP-2 ratio in CSF (but not sera) than the other groups. The CSF/ serum albumin ratio, an index of BBB permeability, was most strongly correlated with CSF MMP-2 concentration, which in turn correlated with CSF interleukin-6 levels. Immunohistochemistry revealed MMP-2- and TIMP-1-positive cells surrounding vessels in NMO lesions. CONCLUSION: In NMO, increased CSF MMP-2, likely induced by interleukin-6 signaling, may disrupt the BBB and enable serum anti-AQP-4 antibodies migration into the central nervous system (CNS).
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Authors | Tomohiko Uchida, Masahiro Mori, Akiyuki Uzawa, Hiroki Masuda, Mayumi Muto, Ryohei Ohtani, Satoshi Kuwabara |
Journal | Multiple sclerosis (Houndmills, Basingstoke, England)
(Mult Scler)
Vol. 23
Issue 8
Pg. 1072-1084
(Jul 2017)
ISSN: 1477-0970 [Electronic] England |
PMID | 27682231
(Publication Type: Journal Article)
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Chemical References |
- Albumins
- Aquaporin 4
- Autoantibodies
- IL6 protein, human
- Interleukin-6
- MMP2 protein, human
- Matrix Metalloproteinase 2
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Topics |
- Adult
- Albumins
(cerebrospinal fluid)
- Aquaporin 4
(cerebrospinal fluid, immunology)
- Autoantibodies
(cerebrospinal fluid)
- Blood-Brain Barrier
- Female
- Humans
- Interleukin-6
(cerebrospinal fluid)
- Male
- Matrix Metalloproteinase 2
(cerebrospinal fluid)
- Middle Aged
- Neuromyelitis Optica
(cerebrospinal fluid, pathology)
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