INT277003

Context Info Confidence 0.47 First Reported 2009 Last Reported 2009 Negated 1 Speculated 0 Reported most in Body Documents 1 Total Number 10 Disease Relevance 3.05 Pain Relevance 0.07

cell differentiation (MUSK) plasma membrane (MUSK)

Anatomy Link Frequency plasma 4 muscle 1 band 1 MUSK (Homo sapiens)

Pain Link Frequency Relevance Heat Multiple sclerosis 10 71.92 tolerance 10 69.84 Calcium channel 20 20.96 anesthesia 10 19.40 rheumatoid arthritis 10 5.00 Inflammation 10 5.00

Disease Link Frequency Relevance Heat Myasthenia Gravis 270 100.00 Disease 190 99.56 Malignant Neoplastic Disease 20 81.88 Hypersensitivity 20 81.28 Demyelinating Disease 10 71.92 Diabetes Mellitus 20 61.36 Autoimmune Disease 50 47.64 Syndrome 10 43.12 Cancer 60 42.40 Neurological Disease 20 35.80

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Having found that all three MuSK-MG plasmas bound to and immunoprecipitated a biotinylated 90-kDa protein, we wished to estimate the quantity of immunoprecipitated protein upon which mass spectrometry identification was to be attempted.

MuSK-MG Binding (bound) of in plasmas associated with myasthenia gravis

1) Confidence 0.47 Published 2009 Journal Molecular & Cellular Proteomics : MCP Section Body Doc Link PMC2716719 Disease Relevance 0.39 Pain Relevance 0

Another subgroup of myasthenia gravis patients has antibodies to a muscle-specific tyrosine kinase (MuSK).1 These antibodies are known to bind to the cell surface and to inhibit the clustering function of MuSK (10).

MuSK Neg (inhibit) Binding (bind) of in muscle associated with myasthenia gravis

2) Confidence 0.47 Published 2009 Journal Molecular & Cellular Proteomics : MCP Section Body Doc Link PMC2716719 Disease Relevance 0.78 Pain Relevance 0

The three MuSK-MG patients' sera bound to the cells at levels higher than the mean + 2 S.D. of the healthy control sera (Fig. 2a).

MuSK-MG Binding (bound) of associated with myasthenia gravis

3) Confidence 0.41 Published 2009 Journal Molecular & Cellular Proteomics : MCP Section Body Doc Link PMC2716719 Disease Relevance 0.18 Pain Relevance 0

l of MuSK-MG plasma (with a maximum MuSK binding capacity of 62 ng) immunoprecipitated ?

MuSK Binding (binding) of in plasma associated with myasthenia gravis

4) Confidence 0.36 Published 2009 Journal Molecular & Cellular Proteomics : MCP Section Body Doc Link PMC2716719 Disease Relevance 0.16 Pain Relevance 0

This preliminary step demonstrated that an IgG antibody in the MuSK-positive plasmas bound to the TE671 cells and that these cells should provide a good starting point for the identification of the antigenic target(s).

MuSK Binding (bound) of in plasmas

5) Confidence 0.36 Published 2009 Journal Molecular & Cellular Proteomics : MCP Section Body Doc Link PMC2716719 Disease Relevance 0.23 Pain Relevance 0

After SDS-PAGE and Western blotting, the unlabeled cell immunoprecipitate was probed with a goat antibody to MuSK, which bound to the same 90-kDa band believed to be MuSK (Fig. 2d).

MuSK Binding (bound) of in band

6) Confidence 0.36 Published 2009 Journal Molecular & Cellular Proteomics : MCP Section Body Doc Link PMC2716719 Disease Relevance 0.39 Pain Relevance 0

However, these immunoprecipitates contained an excess of IgG that was not bound to MuSK but that bound to the protein G-Sepharose, making it very difficult to identify the antigen in subsequent mass spectrometry experiments.

MuSK Binding (bound) of

7) Confidence 0.36 Published 2009 Journal Molecular & Cellular Proteomics : MCP Section Body Doc Link PMC2716719 Disease Relevance 0.31 Pain Relevance 0

l of MuSK-MG plasma (with a maximum MuSK binding capacity of 62 ng) immunoprecipitated ?

MuSK Binding (capacity) of in plasma associated with myasthenia gravis

8) Confidence 0.36 Published 2009 Journal Molecular & Cellular Proteomics : MCP Section Body Doc Link PMC2716719 Disease Relevance 0.16 Pain Relevance 0

Like many pathogenic disease-specific antibodies, MuSK antibodies bind with high affinity to their target MuSK (12).

MuSK Binding (bind) of associated with disease

9) Confidence 0.35 Published 2009 Journal Molecular & Cellular Proteomics : MCP Section Body Doc Link PMC2716719 Disease Relevance 0.37 Pain Relevance 0.04

To establish this method, we used a model system involving the TE671 cell line and MuSK antibodies that are known to bind to MuSK on the TE671 cells.

MuSK Binding (bind) of

10) Confidence 0.35 Published 2009 Journal Molecular & Cellular Proteomics : MCP Section Body Doc Link PMC2716719 Disease Relevance 0.08 Pain Relevance 0.03

General Comments

This test has worked.