Graft vs. host disease

Graft-versus-host disease

Cyclosporine

Why choose this topic?

• Mainly that it relates to a lot of different areas that we have learned about so far in class. Such as the different types of CD4 cells and their functions.

Binds to Cyclosphilins

Inhibits calcineurin

Supresses IL-2 via NFAT not entering nucleus.

Less affective than Tacrolimus

Tacrolimus

Binds to FK protein not allowing calcineurin to dephosphorylate NFAT

Treatment

IL-2 suppression

What are GvHD patients missing?

Work cited

• Treg cells/ Th2 cells
• IL-10
• IL-4

• Barrett, A. J. 1987. Graft-versus-host disease: a review. J. R. Soc. Med. 80, 368–373.
• Chao, N. J. (2017, March). Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease.
• Cyclosporine. (2017, April 16). Retrieved from https://www.drugbank.ca/drugs/DB00091#pharmacology.
• Flinn, A. M., & Gennery, A. R. 2016. Extracoporeal photopheresis treatment of acute graft-versus-host disease following allogeneic haematopoietic stem cell transplantation. F1000Research, 5, F1000 Faculty Rev–1510. http://doi.org/10.12688/f1000research.8118.1.
• H. (Director). (2013, May 19). Immunosuppressive pharmacology Cyclosporine, Tacrolimus, Sirolimus: MTOR, FK, IL2 [Video file]. Retrieved from https://www.youtube.com/channel/UCAfnk12yPoArj0XB37iLWtA
• Mahadeo, K., Masinsin, B., Kapoor, N., Shah, A., Abdel-Azim, H., Parkman, R. 2014. Immunologic resolution of human chronic graft-versus-host disease: Biol. Blood Marrow Transplant 20, 1508-1515.
• O. (2017, April 13). "Graft-Versus-Host Disease" by Christine Duncan for OPENPediatrics. Retrieved from
• Presland, R.B., 2016. Biology of chronic graft-vs-host disease: Immune mechanisms and progress in biomarker discovery. world J. Transplant 6, 608–619
• Prograf (Tacrolimus) Drug Information: Clinical Pharmacology - Prescribing Information at RxList. (2016, December 8). Retrieved from http://www.rxlist.com/prograf-drug/clinical-pharmacology.htm

What is graft-versus-host disease?

How do you diagnose GvHD? (Chao, 2017).

• Skin

- Stage 1. Maculopapular rash on 25% of body.

- Stage 2. Maculopapular rash on 50% of body.

- Stage 3. Erythroderma.

- Stage 4. Erythroderma and bullous formations.

• GI tract

- Stage 1. 500-1000 mL/day .

- Stage 2. 1000-1500 mL/day .

-Stage 3. 15000-2000 mL/day .

- Stage 4. >2000 mL/day.

• Liver, the levels of bilirubin are determined by a liver biopsy.

- Stage 1. 2-3 mg/dL

- Stage 2. 3-6 mg/dL

- Stage 3. 6-15 mg/dL

- Stage 4. > 15 mg/dL

(Chao, 2017).

• Inflammatory disease -(Presland,2016)
• Mainly in the skin about 71% (Presland,2016).
• Occurs about 100 days after transplant (Presland, 2016).

7:25-9:25

Specific biomarkers

Extracorporeal photopheresis (ECP) (Flinn, A., et al., 2016).

(Presland, 2016)

• IL-10
• BAFF
• TNF-alpha
• TNFR-1

• Take cells from blood expose to 8-methoxypsoralen and UVA radiation.
• Causes damage to DNA.
• Dendritic cells phagocytose the damaged cells, renders them more tolerant and they increase in number
• Once the now tolerant dendritic cells interact with T-cells 3 things can happen

- T-cells become anergic

-T-cells commit apoptosis

-T-cells are stimulated to become Treg cells (Flinn, A., et al., 2016).

What do GvHD patients have too much of?

• BAFF (Mahadeo, et al., 2014).
• IL-12
• TNF-alpha (Mahadeo, et al., 2014).
• TH1 cells (Flinn, 2016).
• GM-CSF