INT140413

Context Info Confidence 0.78 First Reported 2006 Last Reported 2010 Negated 13 Speculated 2 Reported most in Body Documents 113 Total Number 147 Disease Relevance 139.25 Pain Relevance 25.53

transport (AQP4) plasma membrane (AQP4) transmembrane transport (AQP4) cytoplasm (AQP4)

Anatomy Link Frequency astrocytes 10 plasma 6 brain 6 M-1 6 spinal cord 4 AQP4 (Homo sapiens)

Pain Link Frequency Relevance Heat intrathecal 596 99.98 Multiple sclerosis 1415 99.88 Spinal cord 782 99.82 Central nervous system 770 99.82 Inflammation 681 99.68 cerebral cortex 65 99.68 Glutamate 864 99.04 addiction 112 98.88 Neuritis 1392 98.56 Demyelination 341 98.48

Disease Link Frequency Relevance Heat Neuromyelitis Optica 8005 100.00 Targeted Disruption 451 99.98 Demyelinating Disease 2807 99.90 Atrophy 224 99.88 Thymoma 6 99.84 Recurrence 1676 99.68 INFLAMMATION 665 99.68 Prion Diseases 192 99.60 Systemic Lupus Erythematosus 355 99.50 Creutzfeldt Jakob Disease 321 99.44

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Key:

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Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

AQP4 autoantibodies from serum of NMO patients bound to AQP4 expressed on thymoma cell membrane.

Gene_expression (expressed) of AQP4

1) Confidence 0.78 Published 2010 Journal J. Neuroimmunol. Section Body Doc Link 20728226 Disease Relevance 0.11 Pain Relevance 0

AIM: We studied the expression of AQP4 by thymoma from patients with and without myasthenia gravis (MG).

Gene_expression (expression) of AQP4

2) Confidence 0.78 Published 2010 Journal J. Neuroimmunol. Section Body Doc Link 20728226 Disease Relevance 0.19 Pain Relevance 0

Serum NMO-IgG autoantibodies (Abs), a specific finding in NMO patients, target the water channel protein aquaporin-4 (AQP4), which is expressed as a long (M-1) or a short (M-23) isoform.

Gene_expression (expressed) of aquaporin-4 in M-1 associated with neuromyelitis optica

3) Confidence 0.78 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2864757 Disease Relevance 1.39 Pain Relevance 0.13

Thus we suggest that only M-23 AQP4 should be used as target antigen for the early detection of AQP4-IgG.

Gene_expression (detection) of AQP4-IgG

4) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2864757 Disease Relevance 0.92 Pain Relevance 0.11

Additionally, serum Abs to full length AQP4 were also detected in the patient with isolated myelitis, but not in the patient with SLE-myelitis, who were both positive for M-23 AQP4-IgG.

Neg (not) Gene_expression (detected) of AQP4 associated with systemic lupus erythematosus and demyelinating disease

5) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2864757 Disease Relevance 2.00 Pain Relevance 0.21

Serum NMO-IgG autoantibodies (Abs), a specific finding in NMO patients, target the water channel protein aquaporin-4 (AQP4), which is expressed as a long (M-1) or a short (M-23) isoform.

Gene_expression (expressed) of AQP4 in M-1 associated with neuromyelitis optica

6) Confidence 0.78 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2864757 Disease Relevance 1.39 Pain Relevance 0.13

However, AQP4-IgM were also detected in a low percentage of patients with MS and OND.

Gene_expression (detected) of AQP4-IgM associated with multiple sclerosis and neurological disease

7) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2864757 Disease Relevance 1.13 Pain Relevance 0.14

In contrast, AQP4-IgG Abs were not present in patients with MS, OND, and non-neuropsychiatric SLE and in HC, which supports their high relevance as biological markers.

Neg (not) Gene_expression (present) of AQP4-IgG associated with multiple sclerosis, neurological disease and systemic lupus erythematosus

8) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2864757 Disease Relevance 2.00 Pain Relevance 0.19

Expression of AQP4 in HEK-293A cells

Gene_expression (Expression) of AQP4

9) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2864757 Disease Relevance 2.39 Pain Relevance 0.85

The target antigen of NMO-IgG was recently identified as aquaporin-4 (AQP4) water channel protein, which is mainly expressed in brain and spinal cord.

Gene_expression (expressed) of aquaporin-4 in spinal cord associated with neuromyelitis optica and spinal cord

10) Confidence 0.77 Published 2006 Journal Tohoku J. Exp. Med. Section Abstract Doc Link 17146196 Disease Relevance 1.31 Pain Relevance 0.14

In the present study, we have established human cell lines that stably express human AQP4 and used these cells to detect and titrate anti-AQP4 antibody present in the sera of patients with NMO by immunofluorescence assay.

Gene_expression (express) of AQP4 associated with neuromyelitis optica

11) Confidence 0.77 Published 2006 Journal Tohoku J. Exp. Med. Section Abstract Doc Link 17146196 Disease Relevance 1.38 Pain Relevance 0.13

JSCK transfected the HEK293 cells with human AQP4 gene and is one of the investigators who interpreted the immunofluorescence results.

Gene_expression (transfected) of AQP4 gene

12) Confidence 0.77 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2941752 Disease Relevance 0 Pain Relevance 0

Transfected HEK 293 cells express human AQP4 homotetramers closely packed on cell membranes [37], and allow detection of AQP4 autoantibodies binding to extracellular epitopes of human AQP4.

Gene_expression (express) of AQP4

13) Confidence 0.77 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2941752 Disease Relevance 1.48 Pain Relevance 0.19

AQP4 autoantibodies seropositivity rates are reported to be higher by IIFA using transfected mammalian cells which express human AQP4 on their cell membranes (cell-based IIFA) than by IIFA using mammalian CNS tissue (tissue-based IIFA).

Gene_expression (express) of AQP4

14) Confidence 0.77 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2941752 Disease Relevance 0.74 Pain Relevance 0.25

Cells were examined under a microscope for green fluorescence over cell membranes from expression of the GFP-AQP4 fusion protein, and stably transfected cells were selected by G418 (Invitrogen) at 1200 ?

Gene_expression (expression) of AQP4

15) Confidence 0.77 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2941752 Disease Relevance 0 Pain Relevance 0

A specific auto-antibody, NMO-IgG, was detected in the serum of NMO patients, and aquaporin-4 water channel protein was detected as its target antigen; aquaporin-4 water channel protein is localized at the end-feet of astrocytes.

Gene_expression (detected) of aquaporin-4 in astrocytes associated with neuromyelitis optica

16) Confidence 0.75 Published 2010 Journal Brain Nerve Section Abstract Doc Link 20844302 Disease Relevance 1.57 Pain Relevance 0.32

Expression of AQP4 in the brain and spinal cord is associated with astrocyte membranes that appose endothelial cell basal membranes.

Gene_expression (Expression) of AQP4 in spinal cord associated with spinal cord

17) Confidence 0.73 Published 2010 Journal BMC Neurol Section Body Doc Link PMC2904295 Disease Relevance 1.85 Pain Relevance 0.46

Several studies have reported that areas of CNS inflammation correlate with expression pattern of AQP4 in NMO [22,23].

Gene_expression (expression) of AQP4 associated with neuromyelitis optica, inflammation and central nervous system

18) Confidence 0.73 Published 2010 Journal BMC Neurol Section Body Doc Link PMC2904295 Disease Relevance 1.99 Pain Relevance 0.52

We recently demonstrated in vitro the pathogenicity of NMO-IgG for nonneural cells transgenically expressing AQP4, and that NMO serum IgM is not AQP4 specific.

Gene_expression (expressing) of AQP4 associated with neuromyelitis optica

19) Confidence 0.71 Published 2008 Journal The Journal of Experimental Medicine Section Body Doc Link PMC2571922 Disease Relevance 1.52 Pain Relevance 0.34

Transport-competent EAAT2 protein is up-regulated in differentiating astrocyte progenitors and in nonneural cells expressing AQP4 transgenically.

Gene_expression (expressing) of AQP4 in astrocyte

20) Confidence 0.71 Published 2008 Journal The Journal of Experimental Medicine Section Abstract Doc Link PMC2571922 Disease Relevance 0.97 Pain Relevance 0.40

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