Transplantation
IgG antibodies constitute an important element of the protective immune response, but can, in some situations, be pathogenic or harmful. By transplanting organs or tissue from one individual to another, the recipient’s immune system is exposed to foreign antigens. The IgG response to “non-self” donor tissues and the resulting immune system activation may prevent patients from receiving life altering therapies, such as organ transplantation.
Kidney Transplantation
Kidney transplantation is a lifesaving treatment for patients with kidney failure, also known as end-stage renal disease (ESRD), a serious condition affecting almost 2.5 million patients worldwide1.
People who progress to ESRD will require renal replacement therapy, which involves either dialysis or kidney transplantation. Patients dependent on dialysis may need several hours of treatment multiple times per week2, which for most patients results in significantly impaired quality of life. Receiving a transplant is life-changing, offering a better quality of life at lower societal cost compared to dialysis.3
Across the U.S. and Europe, approximately 170,000 patients are waiting for a kidney transplant, with over 50,000 new patients added to the kidney transplant waiting list each year (20,000 in European Union and United Kingdom, 32,000 in the U.S.)4 Of these between 10 and 15% are classified as highly sensitized,5 causing them to face extended time on transplant waiting lists due to a broad reactivity against human leukocyte antigens (HLA) that makes the identification of an immunologically suitable donor organ more difficult1,6.
Highly sensitized patients
Transplant patients are classified as highly sensitized when they have donor-specific antibodies (DSAs) with a broad reactivity against human leukocyte antigens (HLAs), which cause an immune response against non-self tissues such as a donor's organ7. These donor-specific antibodies (DSAs) are the result of prior immune response to human leukocyte antigens (HLA) developed through pregnancy, blood transfusions and/or previous transplants7,8. DSAs carry the risk of causing significant tissue damage and potential rejection if they are present at the time of transplantation8.
The presence of DSAs is either an absolute or relative contraindication, depending on the breadth and strength of the antibody response. Due to their presence, highly sensitized patients have longer waiting times without access to a potentially lifesaving kidney transplant within the national allocation system or prioritization programs9,10. Across the U.S. and Europe, highly sensitized patients comprise around 10-15% of transplant waiting lists1,5.
Our commitment to highly sensitized patients
At Hansa Biopharma, we are committed to finding and developing solutions that can help address the unmet medical needs of highly sensitized patients. Our first treatment has been granted conditional authorization by the European Commission in the European Union (EU)/EAA and the United Kingdom (UK) as the first desensitization treatment of highly sensitized adult kidney transplant patients with a positive crossmatch against an available deceased donor11.
Taking care of a transplanted kidney through physical and mental health
“And people say to me: I never would have guessed that you had a kidney transplant… when I hear those words, they keep me motivated, and keep me going.”
Life on tour with chronic kidney disease
“I had always played the guitar and wrote songs but never really did anything with it. Nothing was going to hold me back now! No more excuses… there wasn’t time!”
Antibody-mediated graft rejection
Acute antibody-mediated rejection (AMR) is one of the biggest risks for patients after a transplant. By transplanting organs or tissue from one individual to another, a process known as allogeneic transplantation, the recipient’s immune system is exposed to foreign antigens. As part of a natural immune response against the graft, the immune system can develop donor-specific antibodies, or DSAs, that are specific to the transplant. These DSAs can cause an AMR that may eventually result in an unsuccessful transplantation.
In kidney transplantation, AMR occurs in approximately 5-7%12 of patients and is the main cause for transplants failure.
Reference:
1. Jordan SC, et al. Imlifidase Desensitization in Crossmatch-positive, Highly Sensitized Kidney Transplant Recipients: Results of an International Phase 2 Trial (Highdes). Transplantation. 2021 Aug 1;105(8):1808-1817. doi: 10.1097/TP.0000000000003496.
2. National Institute of Diabetes and Digestive and Kidney Diseases. Hemodialysis. Available at: https://www.niddk.nih.gov/health-information/kidney-disease/kidney-failure/hemodialysis. Last accessed: May 2024.
3. Axelrod DA, et al. An economic assessment of contemporary kidney transplant practice. Am J Transplant. 2018 May;18(5):1168-1176. doi: 10.1111/ajt.14702. Epub 2018 Mar 31. PMID: 29451350.
4. Newsletter Transplant 2022. International figures on donation and transplantation. Available at: Newsletter Transplant - latest edition I Freepub (edgm.eu). Accessed May: 2024.
5. Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2022 Annual Data Report. U.S. Department of Health and Human Services, Health Resources and Services Administration; 2024. Accessed: May 2024 date.
6. ESOT Transplantation Learning Journey Highlights 15-17 November 2020-pg 25. Available at https://esot.org/scientific-highlights-transplantation-learning-journey-tlj-2-0/ Last accessed: May 2024
7. Mamode N, et al. European Guideline for the Management of Kidney Transplant Patients With HLA Antibodies: By the European Society for Organ Transplantation Working Group. Transpl Int. 2022 Aug 10;35:10511. Available at: https://pubmed.ncbi.nlm.nih.gov/36033645/
8. Eurostam Report (A Europe-wide strategy to enhance transplantation of highly sensitized patients on the basis of acceptable HLA mismatches.) Available at https://cordis.europa.eu/project/id/305385/reporting. Last accessed: May 2024
9. Redfield RR, et al. The mode of sensitization and its influence on allograft outcomes in highly sensitized kidney transplant recipients. Nephrol Dial Transplant. 2016 Oct;31(10):1746-53. doi: 10.1093/ndt/gfw099. Epub 2016 Jul 6. PMID: 27387475.
10. Lonze BE, et al. IdeS (Imlifidase): A Novel Agent That Cleaves Human IgG and Permits Successful Kidney Transplantation Across High-strength Donor-specific Antibody. Ann Surg. 2018 Sep;268(3):488-496. doi: 10.1097/
11. European Medicines Agency. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/idefirix. Last accessed: November 2021.
12. Puttarajappa C, et al. Antibody-mediated rejection in kidney transplantation: a review. J Transplant. 2012;2012:193724. doi: 10.1155/2012/193724.
