High Risk of Sensitization After Failed Islet Transplantation
Open accessAbstract
Human Leukocyte Antigen (HLA) antibodies posttransplant have been associated with an increased risk of early graft failure in kidney transplants. Whether this also applies to islet transplantation is not clear. To achieve insulin independence after islet transplants multiple donor infusions may be required. Hence, islet transplant recipients are at risk of sensitization after transplantation. Islet transplant recipients were screened for HLA antibodies posttransplant by flow-based methods. A total of 98 patients were studied. Twenty-nine patients (31%) developed de novo donor specific antibodies (DSA) posttransplant. Twenty-three patients developed DSA while on immunosuppression (IS). Among recipients who have discontinued IS, 10/14 (71%) are broadly sensitized with panel reactive antibody (PRA) >or=50%. The risk of becoming broadly sensitized after transplant was 11/69 (16%) if the recipient was unsensitized prior to transplant. The majority of these antibodies have persisted over time. Appearance of HLA antibodies posttransplant is concerning, and the incidence rises abruptly in subjects weaned completely from IS. This may negatively impact the ability of these individuals to undergo further islet, pancreas or kidney transplantation and should be discussed upfront during evaluation of candidates for islet transplantation.
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Transplanting cells from multiple genetic backgrounds per patient could exacerbate immune rejection and graft failure.
“Not only are the number of pancreases available for islet isolation limited, but transplanting cells from multiple genetic backgrounds per patient could exacerbate immune rejection and graft failure.25,26”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [25]
The Introduction (page unavailable) says that islets from multiple donors are often needed and that HLA mismatches may lead to antibodies. The Discussion (page unavailable) links multiple mismatches to broad sensitization, but says the role of these antibodies in islet graft failure is difficult to prove. The paper therefore supports the immune-risk concern, not a demonstrated link from multiple donors to rejection and graft failure. (LLM, conf=0.84)
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Research works printed but not linked: 18
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- Authors
- Campbell, P. M., Senior, P. A., Salam, A., LaBranche, K., Bigam, D. L., Kneteman, N. M., Imes, S., Halpin, A., Ryan, E. A., & Shapiro, A. M. J.
- Affiliations
- University of Alberta (CA)
- Corresponding author
- Campbell, P.M
- Venue
- American Journal of Transplantation
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 7
- Issue
- 10
- Pages
- 2311-2317
- ISSN
- 1600-6135 (ISSN-L)
- OpenAlex
- W2154507669
- Cited by
- 173
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 8 · 2022: 5 · 2021: 4 · 2020: 6 · 2019: 3 · 2018: 7 · 2017: 2 · 2016: 9 · 2015: 7 · 2014: 13 · 2013: 13 · 2012: 16
- FWCI
- 20.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal of Transplantation (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK059101, DK59101)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- islet transplantation, HLA antibodies, donor-specific antibodies, sensitization, panel reactive antibody, immunosuppression withdrawal, graft failure, insulin independence, type 1 diabetes, transplant evaluation
- MeSH terms
- C-Peptide, Histocompatibility Testing, HLA Antigens, HLA-DR Antigens, Humans, Immunization, Isoantibodies, T-Lymphocytes, HLA-A Antigens, HLA-B Antigens, Islets of Langerhans Transplantation, Treatment Failure
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