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Another #immunosuppression #tweetorial...spotlight today on #belatacept today
How do you say it? @Babybel @MedTweetorials
Another #immunosuppression #tweetorial...spotlight today on #belatacept today
How do you say it? @Babybel @MedTweetorials
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Belatacept is the FUSION protein that has been the @NKOTB in #kidneytransplant - having been approved for use in 2011.
What's fused?
1. Human IgG1 Fc fragment
2. Extracellular domain of cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4)
https://pubmed.ncbi.nlm.nih.gov/25416857/
Belatacept is the FUSION protein that has been the @NKOTB in #kidneytransplant - having been approved for use in 2011.
What's fused?
1. Human IgG1 Fc fragment
2. Extracellular domain of cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4)
https://pubmed.ncbi.nlm.nih.gov/25416857/
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The goal of this fusion protein? Disrupt Signal
of the 
-Signal T-cell activation pathway
Signal 2 = Binding of CD28 (on T-cell) to B7-1/B7-2 (on APC)
This important step is called co-stimulation and is necessary for T-cell activation
https://www.nejm.org/doi/full/10.1056/nejmra033540
The goal of this fusion protein? Disrupt Signal
of the -Signal T-cell activation pathwaySignal 2 = Binding of CD28 (on T-cell) to B7-1/B7-2 (on APC)
This important step is called co-stimulation and is necessary for T-cell activation
https://www.nejm.org/doi/full/10.1056/nejmra033540
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Worth saying again that co-stimulation is a necessary step for T-cell activation.
https://www.kidney-international.org/article/S0085-2538(15)55444-6/fulltext
Worth saying again that co-stimulation is a necessary step for T-cell activation.
https://www.kidney-international.org/article/S0085-2538(15)55444-6/fulltext
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Back to CTLA-4 (AKA CD 152) - it's expressed by T-cells, and binding of CTLA-4 to B7-1/B7-2 on APC acts T-cell activation inhibitor
So...binding of #belatacept to B7-1/B7-2 (AKA CD 80/86) prevents this important co-stimulatory binding step.
https://pubmed.ncbi.nlm.nih.gov/24100403/
Back to CTLA-4 (AKA CD 152) - it's expressed by T-cells, and binding of CTLA-4 to B7-1/B7-2 on APC acts T-cell activation inhibitor
So...binding of #belatacept to B7-1/B7-2 (AKA CD 80/86) prevents this important co-stimulatory binding step.
https://pubmed.ncbi.nlm.nih.gov/24100403/
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Belatacept is given as a monthly, intravenous infusion and can be used in #immunosuppression regimens to spare the #kidneytransplant recipient of the MANY notorious #CNI adverse effects: https://twitter.com/ssfarouk/status/1143320493585571840?s=20
Belatacept is given as a monthly, intravenous infusion and can be used in #immunosuppression regimens to spare the #kidneytransplant recipient of the MANY notorious #CNI adverse effects: https://twitter.com/ssfarouk/status/1143320493585571840?s=20
7/ The 2016 BENEFIT phase-3 study found that 7 yrs after #kidneytransplant...
Pt AND graft survival AND mean eGFR were significantly higher with #belatacept (compared to cyclosporine)
https://www.nejm.org/doi/full/10.1056/nejmoa1506027
Pt AND graft survival AND mean eGFR were significantly higher with #belatacept (compared to cyclosporine)
https://www.nejm.org/doi/full/10.1056/nejmoa1506027
8/ Here's a tweet for big sibling abatacept - which differs from belatacept by only 2 amino acids
Abatacept has been used for the treatment of #rheumatoid arthritis since the early 2000s
https://pubmed.ncbi.nlm.nih.gov/14614165/
Belatacept has
affinity for B7-1/2, compared to its older sib
Abatacept has been used for the treatment of #rheumatoid arthritis since the early 2000s
https://pubmed.ncbi.nlm.nih.gov/14614165/
Belatacept has
affinity for B7-1/2, compared to its older sib
9/ Check out more #belatacept clinical trials at @RenalFellowNtwk
https://www.renalfellow.org/2019/07/27/landmark-trials-of-belatacept-in-kidney-transplantation/
Though some studies found increased rates of rejection in the bela groups, overall outcomes were not affected
https://www.renalfellow.org/2019/07/27/landmark-trials-of-belatacept-in-kidney-transplantation/
Though some studies found increased rates of rejection in the bela groups, overall outcomes were not affected
10/
A word of caution:
Avoid #belatacept in Epstein-Barr Virus (EBV) seronegative patients, as higher incidence of post-transplant lymphoproliferative disorder was seen in #BENEFIT
A word of caution:
Avoid #belatacept in Epstein-Barr Virus (EBV) seronegative patients, as higher incidence of post-transplant lymphoproliferative disorder was seen in #BENEFIT
11/ In summary:
-Belatacept is a fusion protein of: Fc fragment of human IgG1 + part of CTLA-4
-It inhibits the co-stimulatory T-cell activation step (CD28 + B7-1/2)
-Studies have shown improved #kidneytransplant outcomes with bela (compared to #CNI)
-Avoid it if EBV sero (-)
-Belatacept is a fusion protein of: Fc fragment of human IgG1 + part of CTLA-4
-It inhibits the co-stimulatory T-cell activation step (CD28 + B7-1/2)
-Studies have shown improved #kidneytransplant outcomes with bela (compared to #CNI)
-Avoid it if EBV sero (-)
