INT186126

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Context Info
Confidence 0.52
First Reported 2005
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 9
Total Number 9
Disease Relevance 4.13
Pain Relevance 3.12

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

plasma membrane (CD28, CTLA4) cytosol (CD28) Golgi apparatus (CTLA4)
Anatomy Link Frequency
CD86 3
T-cell 3
hinge 2
CD28 (Homo sapiens)
CTLA4 (Homo sapiens)
Pain Link Frequency Relevance Heat
abatacept 146 99.04 Very High Very High Very High
psoriasis 109 96.12 Very High Very High Very High
rheumatoid arthritis 96 95.84 Very High Very High Very High
cytokine 90 95.68 Very High Very High Very High
Arthritis 224 87.80 High High
tolerance 12 78.32 Quite High
metalloproteinase 4 74.96 Quite High
withdrawal 7 70.48 Quite High
Inflammation 102 67.04 Quite High
methotrexate 41 40.48 Quite Low
Disease Link Frequency Relevance Heat
Psoriasis 127 96.12 Very High Very High Very High
Rheumatoid Arthritis 96 95.84 Very High Very High Very High
Autoimmune Disease 26 95.24 Very High Very High Very High
Hookworm Infection 35 94.88 High High
Infection 52 89.68 High High
Seronegative Spondarthritis 96 87.80 High High
Toxicity 11 87.72 High High
Skin Cancer 111 87.36 High High
Adhesions 14 86.24 High High
Leukocytosis 1 85.08 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
CTLA-4 binds to CD80 and CD86 with higher avidity than CD28, thus preventing co-stimulation through this pathway, and is a major down-regulatory signal for T cells.
CD28 Binding (binds) of CTLA-4 in CD86
1) Confidence 0.52 Published 2008 Journal Annals of the Rheumatic Diseases Section Body Doc Link PMC2569144 Disease Relevance 0.52 Pain Relevance 0.52
The most important ligand is CTLA-4, a well-defined down-regulator of T-cell activation, which has a much higher binding affinity for CD80/CD86 than CD28.
CD28 Binding (affinity) of CTLA-4 in T-cell
2) Confidence 0.29 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727897 Disease Relevance 0.36 Pain Relevance 0.68
Thus, in abatacept, a series of directed cysteine to serine mutations were introduced in the hinge region to reduce this Fc- mediated binding.21 Although abatacept proved to be highly efficacious for autoimmune T cell-mediated autoimmune disorders, such as rheumatoid arthritis and psoriasis, it was found to be an inadequate maintenance immunosuppressive agent in nonhuman primate models of transplantation.22–24 Studies into potential reasons for this disconnect found that although CTLA4 binds with a much higher avidity to CD80 and CD86 than does CD28, CTLA4-Ig was significantly less potent at inhibiting CD86-dependent as opposed to CD80-dependent costimulation.25
CD28 Binding (binds) of CTLA4-Ig in hinge associated with psoriasis, autoimmune disease, rheumatoid arthritis and abatacept
3) Confidence 0.23 Published 2010 Journal Drug Design, Development and Therapy Section Body Doc Link PMC2998809 Disease Relevance 0.29 Pain Relevance 0.39
Thus, in abatacept, a series of directed cysteine to serine mutations were introduced in the hinge region to reduce this Fc- mediated binding.21 Although abatacept proved to be highly efficacious for autoimmune T cell-mediated autoimmune disorders, such as rheumatoid arthritis and psoriasis, it was found to be an inadequate maintenance immunosuppressive agent in nonhuman primate models of transplantation.22–24 Studies into potential reasons for this disconnect found that although CTLA4 binds with a much higher avidity to CD80 and CD86 than does CD28, CTLA4-Ig was significantly less potent at inhibiting CD86-dependent as opposed to CD80-dependent costimulation.25
CD28 Binding (binds) of CTLA4 in hinge associated with psoriasis, autoimmune disease, rheumatoid arthritis and abatacept
4) Confidence 0.23 Published 2010 Journal Drug Design, Development and Therapy Section Body Doc Link PMC2998809 Disease Relevance 0.29 Pain Relevance 0.39
CTLA-4, a natural inhibitor of CD28, binds to CD80/86 molecules with high affinity and competes with CD28.
CD28 Binding (competes) of CTLA-4
5) Confidence 0.15 Published 2005 Journal J Immune Based Ther Vaccines Section Body Doc Link PMC1208938 Disease Relevance 0.76 Pain Relevance 0.36
Because CD152 has a high affinity for CD80 and CD86, soluble forms of CTLA4 inhibit the interaction of CD28 with its ligands.
CD28 Neg (inhibit) Binding (interaction) of CTLA4 in CD86
6) Confidence 0.15 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC2833981 Disease Relevance 0.77 Pain Relevance 0.32
As an inhibitor of the immune response, CTLA4 is expressed only on activated T cells and possesses a higher binding affinity for B7 than CD28.


CD28 Binding (affinity) of CTLA4 in T cells
7) Confidence 0.09 Published 2008 Journal Indian Journal of Pharmacology Section Body Doc Link PMC2792605 Disease Relevance 0.36 Pain Relevance 0.33
The T-cell surface protein, CTLA4, competes with CD28 for B7, and binding of CTLA4 to B7 inhibits T-cell proliferation and the elaboration of immune stimulatory cytokines.
CD28 Binding (competes) of CTLA4 in T-cell associated with cytokine
8) Confidence 0.07 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004577 Disease Relevance 0.36 Pain Relevance 0.09
CTLA-4 directly competes with CD28 for binding CD80/CD86 (B7) and also directs the assembly of inhibitory signaling complexes that lead to cell quiescence or anergy [48].
CD28 Binding (competes) of CTLA-4 in CD86
9) Confidence 0.06 Published 2009 Journal PLoS Neglected Tropical Diseases Section Body Doc Link PMC2654967 Disease Relevance 0.42 Pain Relevance 0.03

General Comments

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