INT155484

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Context Info
Confidence 0.52
First Reported 2003
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 15
Total Number 16
Disease Relevance 8.85
Pain Relevance 6.09

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 (CD86, CTLA4) Golgi apparatus (CTLA4) cell-cell signaling (CD86)
Anatomy Link Frequency
CD86 8
T-cell 4
hinge 2
cytotoxic T-lymphocyte 2
CD86 (Homo sapiens)
CTLA4 (Homo sapiens)
Pain Link Frequency Relevance Heat
abatacept 524 96.80 Very High Very High Very High
psoriasis 37 96.12 Very High Very High Very High
rheumatoid arthritis 380 95.84 Very High Very High Very High
Arthritis 327 87.80 High High
Pain 12 84.68 Quite High
tolerance 46 80.64 Quite High
Inflammation 238 77.56 Quite High
metalloproteinase 8 74.96 Quite High
adenocard 6 74.60 Quite High
cytokine 172 73.76 Quite High
Disease Link Frequency Relevance Heat
Adhesions 19 98.88 Very High Very High Very High
Psoriasis 37 96.12 Very High Very High Very High
Rheumatoid Arthritis 382 95.84 Very High Very High Very High
Autoimmune Disease 87 95.24 Very High Very High Very High
Apoptosis 14 93.08 High High
Disease 292 89.52 High High
Arthritis 112 87.80 High High
Immunization 4 86.60 High High
Graft Vs Host Disease 8 86.56 High High
Organ Transplantation 11 85.48 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.
CD86 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 0.51
These data suggest a novel role for CD86 expression on the microvasculature, whereby ligation of CTLA-4 on CD4 T cells by CD86 on islet ECs is key to the adhesion of recently activated T cells.
CD86 Binding (ligation) of CTLA-4 in T cells associated with adhesions
2) Confidence 0.45 Published 2008 Journal J. Immunol. Section Abstract Doc Link 18941200 Disease Relevance 0.48 Pain Relevance 0.12
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.
CD86 Binding (affinity) of CTLA-4 in T-cell
3) Confidence 0.43 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727897 Disease Relevance 0.36 Pain Relevance 0.67
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
CD86 Binding (binds) of CTLA4-Ig in hinge associated with psoriasis, autoimmune disease, rheumatoid arthritis and abatacept
4) Confidence 0.35 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
CD86 Binding (binds) of CTLA4 in hinge associated with psoriasis, autoimmune disease, rheumatoid arthritis and abatacept
5) Confidence 0.35 Published 2010 Journal Drug Design, Development and Therapy Section Body Doc Link PMC2998809 Disease Relevance 0.29 Pain Relevance 0.39
To address the poor outcomes in transplantation studies, further development of CTLA4-Ig concentrated on improving its binding to CD86 in particular (owing to its importance in initiation of the immune reaction in primates), in order to confer the more potent immunosuppressive action needed.
CD86 Binding (binding) of CTLA4-Ig in CD86
6) Confidence 0.25 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2582812 Disease Relevance 1.04 Pain Relevance 0.49
This led to the development of belatacept, a second-generation CTLA4-Ig that exhibits superior binding to CD80 and CD86 as compared with the parent CTLA4-Ig.


CD86 Binding (binding) of CTLA4-Ig in CD86
7) Confidence 0.22 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2582812 Disease Relevance 1.21 Pain Relevance 0.76
Because CD152 has a high affinity for CD80 and CD86, soluble forms of CTLA4 inhibit the interaction of CD28 with its ligands.
CD86 Binding (affinity) of CD152 in CD86
8) Confidence 0.16 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC2833981 Disease Relevance 0.81 Pain Relevance 0.31
Because CD152 has a high affinity for CD80 and CD86, soluble forms of CTLA4 inhibit the interaction of CD28 with its ligands.
CD86 Binding (affinity) of CTLA4 in CD86
9) Confidence 0.16 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC2833981 Disease Relevance 0.77 Pain Relevance 0.32
Wing et al. described the role of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a protein highly expressed by Tregs, which inhibits the immune response [39]; CTLA-4 binds the costimulatory molecules CD80 (B7-1) and CD86 (B7-2) with higher affinity than CD28, inhibiting the second signal, necessary to immune activation [40].
B7-2 Binding (binds) of CTLA-4 in cytotoxic T-lymphocyte
10) Confidence 0.15 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2821644 Disease Relevance 0.43 Pain Relevance 0.23
Wing et al. described the role of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a protein highly expressed by Tregs, which inhibits the immune response [39]; CTLA-4 binds the costimulatory molecules CD80 (B7-1) and CD86 (B7-2) with higher affinity than CD28, inhibiting the second signal, necessary to immune activation [40].
CD86 Binding (binds) of CTLA-4 in cytotoxic T-lymphocyte
11) Confidence 0.15 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2821644 Disease Relevance 0.43 Pain Relevance 0.23
Cytotoxic T-cell Lymphocyte Antigen-4 (CTLA4) bears structural similarity to CD28, but has much higher affinity for CD80 and CD86 (Bluestone et al 2006).
CD86 Binding (affinity) of CTLA4 in CD86
12) Confidence 0.12 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721362 Disease Relevance 0.59 Pain Relevance 0.63
Cytotoxic T-cell Lymphocyte Antigen-4 (CTLA4) bears structural similarity to CD28, but has much higher affinity for CD80 and CD86 (Bluestone et al 2006).
CD86 Binding (affinity) of T-cell Lymphocyte Antigen-4 in CD86
13) Confidence 0.12 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721362 Disease Relevance 0.64 Pain Relevance 0.64
Shortly after activation has occurred the T-cell then expresses a number of other co-stimulatory molecules including CTLA4, which is homologous to CD28 but binds CD80 and CD86 with higher affinity (Linsley et al 1991).
CD86 Binding (binds) of CTLA4 in T-cell
14) Confidence 0.12 Published 2006 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1936358 Disease Relevance 0.40 Pain Relevance 0.16
This led to the development of belatacept (LEA29Y), a modified version of CTLA4-Ig with greater affinity to CD80 and CD86 that is conveniently administered monthly [134].
CD86 Binding (affinity) of CTLA4-Ig in CD86
15) Confidence 0.05 Published 2009 Journal Journal of Transplantation Section Body Doc Link PMC2809333 Disease Relevance 0.21 Pain Relevance 0.10
The B7 costimulatory pathway involves at least two molecules, B7-1 (CD80) and B7-2 (CD86), on antigen-presenting cells, both of which can interact with their counter-receptors, CD28 and CTLA-4, on T cells [2].
CD86 Binding (interact) of CTLA-4 in T cells
16) Confidence 0.00 Published 2003 Journal Arthritis Res Ther Section Body Doc Link PMC165060 Disease Relevance 0.37 Pain Relevance 0.11

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