Transplantation of stem cells or other vital organs in the body is one of the only treatment options to increase one’s quality of life and enhance one’s survival for patients with life ending organ failure, blood diseases, or bone marrow diseases. When finding a “match” in transplantation, one of the largest aspects to ensure the acceptance of the transplant is that of the MHC molecule or the HLA molecule in humans. The HLA molecule is essential for initiating the adaptive immune response by presenting antigen peptides to the two types of T cells: Helper T cells (enhance the immune response) and Cytotoxic T cells (kill all infected cells). There are hundreds of thousands of different variant types of HLA molecules that exist all over the world. However, all hope of finding their match isn’t lost as these can be inherited to have similar HLA molecules that decreases the transplantee’s chances of rejection. The catch is that without your body’s particular HLA molecule, any others will be recognized as a foreign object and therefore the body attacks the organ with this foreign HLA molecule. This leads to the acute or chronic rejection of the transplant and therefore the death of the patient. With HLA molecules being so specific, how can physicians reduce this very high chance of rejection? Upon transplantation, the immune system has to be suppressed to basically absence of the immune response altogether through the use of a variety of immunosuppression pharmaceuticals. The immune system is therefore suppressed for the rest of the patient’s life, putting them at very high risk for infectious diseases with a potential of not being able to fight these infections off. Many of these transplant patients will die from the rejection of the transplant or from an infection.
Because this isn’t the most efficient way in enhancing one’s quality of life or the chance of an enhanced survival rate long term, there is also an ongoing clinical treatment trial in rats where the donor rat’s MHC antigens are extracted. They then dilute these molecules into smaller values and inject them into the transplantee rat. The more injections that are given to the patient have more MHC molecules of the donor to help reduce the chances of rejection. However the optimal dosage of these MHC molecules to inject into the rats is still yet to be found. However, the question that we all have is will this be efficient in humans?
I find the induction of the MHC antigens to build an initial tolerance super interesting! In another article that I found (Opelz, G., & Terasaki, P. I. (1978). Improvement of kidney-graft survival with increased numbers of blood transfusions. New England Journal of Medicine, 299(15), 799-803.), rather than using donor cells to begin the tolerance they used myoblasts and myotubes that were genetically modified to express the MHC antigen they wanted. Could this be a useful strategy to combat against rejection?
ReplyDeleteI was looking around on PubMed for some articles talking about other ways to nullify transplant rejection and I came across one that had some interesting information. Apparently, there has been work on inducing preoperative antigen-specific tolerance through gene transfection techniques. By transfecting genes that contain donor major histocompatibility complex (MHC) antigens to recipients before surgery, recipient immune systems are primed to not attack donor antigens, prolonging allografts for the new host. Seems like there are other methods other than immune system suppression that are in the works!
ReplyDeleteChandler, C., & Passaro, E., Jr (1993). Transplant rejection. Mechanisms and treatment. Archives of surgery (Chicago, Ill. : 1960), 128(3), 279–283. https://doi.org/10.1001/archsurg.1993.01420150033006
Hey there,
ReplyDeleteGreat article. I did research with the Regis University School of Pharmacy and the Regis University Biochemistry Department on something similar. We looked into the metabolic pathways of primary myelofibrosis (rare cancer in the bone marrow) and paired this with pharmaceutical interventions for symptom relief and possible reversible splenomagy (enlarged spleen). One of the very last steps of intervention for a patient with PMF is a bone marrow transplant!
I enjoyed reading your blog and your article with my previous knowledge of PMF. Transplants are always risky, but when everything works well - there are great patient outcomes.
If you're interested, I've listed an article referring to the diagnosis checklist for PMF with its treatments and interventions.
Tefferi A. (2021). Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. American journal of hematology, 96(1), 145–162. https://doi.org/10.1002/ajh.26050
Let me know what you think!!