INT145986

Context Info Confidence 0.56 First Reported 2007 Last Reported 2010 Negated 2 Speculated 0 Reported most in Body Documents 8 Total Number 9 Disease Relevance 2.66 Pain Relevance 0.82

Golgi apparatus (CTLA4) plasma membrane (CTLA4)

Anatomy Link Frequency B cells 2 T cell 2 CTLA4 (Homo sapiens)

Pain Link Frequency Relevance Heat abatacept 10 99.94 tolerance 24 99.80 Bile 67 97.44 corticosteroid 5 95.60 cytokine 91 86.88 Inflammation 118 86.48 Neuritis 1 59.92 Inflammatory stimuli 20 5.00 fibrosis 16 5.00 pruritus 14 5.00

Disease Link Frequency Relevance Heat Cancer 14 99.68 Adhesions 5 98.82 Biliary Liver Cirrhosis 246 95.98 Bladder Cancer 1 90.24 Gallstones 23 89.92 INFLAMMATION 138 86.48 Pancreatitis 5 84.32 Systemic Lupus Erythematosus 4 80.12 Diabetes Mellitus 6 78.80 Autoimmune Disease 31 77.44

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

RESULTS: We found a significant increase in CTLA4 49A carriers in patients with AIP compared with healthy individuals (78.3% vs 48%; P <0.0001).

Positive_regulation (increase) of CTLA4

1) Confidence 0.56 Published 2007 Journal Clin. Chem. Section Body Doc Link 17712006 Disease Relevance 0.08 Pain Relevance 0

In a skin transplant model, blockade of the CTLA-4 pathway abolishes immuno-regulation by CD4+CD25+ T-cells, suggesting that CTLA-4 is required for tolerance (Kingsley et al 2002).

Positive_regulation (required) of CTLA-4 in T-cells associated with tolerance

2) Confidence 0.43 Published 2007 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721321 Disease Relevance 0 Pain Relevance 0.05

Some investigators suggest that irAEs occur in the same patients who have anti-tumor responses as a result of the anti-CTLA-4 antibody.

Positive_regulation (result) of CTLA-4 associated with cancer

3) Confidence 0.42 Published 2008 Journal Cancer Immun. Section Abstract Doc Link 18503261 Disease Relevance 0.64 Pain Relevance 0.25

Identical results were obtained for T cell adhesion using either CTLA-4 blocking mAb or CTLA-4Ig (abatacept), indicating CTLA-4 as the T cell ligand for these CD86-mediated effects.

Positive_regulation (indicating) of CTLA-4 in T cell associated with abatacept and adhesions

4) Confidence 0.42 Published 2008 Journal J. Immunol. Section Abstract Doc Link 18941200 Disease Relevance 0.52 Pain Relevance 0.16

A very mild increase in CTLA4 was observed with BMMSCs but the effect was not as striking as in the case of WJMSCs (Figure 4B {i}).

Positive_regulation (increase) of CTLA4

5) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2814860 Disease Relevance 0 Pain Relevance 0.03

Strikingly, co-culture with WJMSCs resulted in an early activation of a negative co-stimulatory molecule, CTLA4, which was not evident with BMMSCs.

Positive_regulation (activation) of CTLA4

6) Confidence 0.25 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2814860 Disease Relevance 0.40 Pain Relevance 0.29

In 258 PBC patients and two independent control groups of 286 and 269 healthy volunteers, the authors investigated distribution of newly identified htSNPs of 15 selected candidate genes: two related to immunity encoding for CTLA-4 and TNF?

Positive_regulation (encoding) of CTLA-4 associated with biliary liver cirrhosis

7) Confidence 0.11 Published 2009 Journal Semin Immunopathol Section Body Doc Link PMC2758170 Disease Relevance 1.01 Pain Relevance 0.05

RESULTS: In contrast to unmodified CTLA4-Ig, abatacept did not mediate CDC or ADCC of target B cells.

Neg (not) Positive_regulation (mediate) of CTLA4-Ig in B cells

8) Confidence 0.05 Published 2007 Journal J. Rheumatol. Section Body Doc Link 17787038 Disease Relevance 0 Pain Relevance 0

RESULTS: In contrast to unmodified CTLA4-Ig, abatacept did not mediate CDC or ADCC of target B cells.

Neg (not) Positive_regulation (mediate) of CTLA4-Ig in B cells

9) Confidence 0.05 Published 2007 Journal J. Rheumatol. Section Body Doc Link 17787038 Disease Relevance 0 Pain Relevance 0

General Comments

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