Usage Information
Abstract
Natural killer (NK) cells respond to diseased and allogeneic cells through NKG2A/HLA-E or killer cell immunoglobulin-like receptor (KIR)/HLA-ABC interactions. Correlations between HLA/KIR disparities and kidney transplant pathology suggest an antibody-independent pathogenic role for NK cells in transplantation, but the mechanisms remain unclear. Using CyTOF to characterize recipient peripheral NK cell phenotypes and function, we observed diverse NK cell subsets among participants who responded heterogeneously to allo-stimulators. NKG2A+KIR+ NK cells responded more vigorously than other subsets, and this heightened response persisted after kidney transplantation despite immunosuppression. In test and validation sets from 2 clinical trials, pretransplant donor-induced release of cytotoxicity mediator Ksp37 by NKG2A+ NK cells correlated with reduced long-term allograft function. Separate analyses showed that Ksp37 gene expression in allograft biopsies lacking histological rejection correlated with death-censored graft loss. Our findings support an antibody-independent role for NK cells in transplant injury and support further testing of pretransplant, donor-reactive, NK cell–produced Ksp37 as a risk-assessing, transplantation biomarker.
Authors
Dan Fu Ruan, Miguel Fribourg, Yuko Yuki, Yeon-Hwa Park, Maureen P. Martin, Haocheng Yu, Geoffrey C. Kelly, Brian Lee, Ronaldo M. de Real, Rachel Lee, Daniel Geanon, Seunghee Kim-Schulze, Nicholas Chun, Paolo Cravedi, Mary Carrington, Peter S. Heeger, Amir Horowitz
Usage data is cumulative from December 2024 through December 2025.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 2,070 | 291 |
| 325 | 77 | |
| Figure | 417 | 0 |
| Table | 53 | 0 |
| Supplemental data | 147 | 14 |
| Citation downloads | 110 | 0 |
| Totals | 3,122 | 382 |
| Total Views | 3,504 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
