Impact of preformed donor-specific anti-HLA antibodies on pancreatic islet transplantation outcomes: do they matter as they do in solid organ transplantation?

BACKGROUND: Preformed 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. METHODS: We 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. RESULTS: The 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. CONCLUSIONS: The 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.