Thread by @ssfarouk

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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)

pubmed.ncbi.nlm.nih.gov/25416857/

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The goal of this fusion protein? Disrupt Signal 2⃣ of the 3⃣-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

nejm.org/doi/full/10.10…

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Worth saying again that co-stimulation is a necessary step for T-cell activation.

kidney-international.org/article/S0085-…

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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.

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

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)

nejm.org/doi/full/10.10…

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

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

renalfellow.org/2019/07/27/lan…

Though some studies found increased rates of rejection in the bela groups, overall outcomes were not affected

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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 (-)