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Impact of preformed donor-specific anti-HLA antibodies on pancreatic islet transplantation outcomes: do they matter as they do in solid organ transplantation?
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DOI：10.3389/fimmu.2026.1909238.png)
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Abstract
En 中文
BackgroundPreformed donor-specific anti-HLA antibodies (DSA) are a major risk factor for antibody-mediated rejection and graft failure in kidney; heart; lung; and other vascularized solid organ transplants. Their clinical significance in pancreatic islet transplantation; however; remains uncertain.MethodsWe conducted a SANRA-guided narrative review using a focused PubMed search (January 1; 2000; to June 9; 2026) supplemented by citation chasing. Of 104 records identified; 11 directly evaluating islet transplantation formed the core evidence base; complemented by 38 references providing mechanistic; immunologic; and solid-organ context.ResultsThe available islet-specific evidence is dominated by small single-center studies; registry analyses; and case series; with few reports directly evaluating preformed DSA. Across these reports; preformed DSA have not shown the consistent adverse effect expected from kidney transplantation; but the evidence is insufficient to establish safety. In the largest focused cohort; Piemonti et al. reported no clear association between preformed DSA and graft failure; whereas post-transplant antibody evolution was more closely linked to impaired graft survival. Brooks et al. similarly found rapid graft dysfunction after de novo DSA; while Pouliquen et al. observed late de novo DSA without uniform graft loss. Registry and failure cohorts show that post-transplant allosensitization is clinically important; especially after immunosuppression withdrawal or repeat transplantation. A proposed mechanistic model is that portal infusion; low tissue mass; early instant blood-mediated inflammatory reaction; endothelial replacement; and non-vascularized graft architecture may reduce the immediate impact of pre-existing DSA while leaving the graft vulnerable to evolving humoral memory.ConclusionsThe limited evidence is insufficient to support a universal policy of automatic exclusion of otherwise suitable islet candidates solely because of low-level preformed DSA; nor does it establish that such antibodies are safe. Because the evidence derives mainly from small single-center cohorts; registry analyses; and case series; this conclusion is provisional and may not be generalized across programs. De novo DSA represent a distinct post-transplant risk and may be a more clinically informative warning signal. Standardized MFI interpretation; complement-binding assays; longitudinal monitoring; and harmonized outcomes are needed.
Keywords:
type 1 diabetes
allosensitization
antibody-mediated rejection
de novo DSA
pancreatic islet transplantation
anti-HLA antibody
donor-specific antibody
preformed DSA
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