ANTIBODY-mediated rejection (ABMR) after kidney transplantation may soon be identified earlier through a new functional immune assay that directly measures natural killer (NK) cell activity, according to emerging research.
The findings suggest the Natural Killer–Cellular Humoral Activation Test (NK-CHAT) could provide clinicians with a non-invasive biomarker for detecting immune-mediated graft injury before irreversible damage occurs.
Why Antibody-Mediated Rejection Remains a Major Challenge
ABMR is one of the leading causes of long-term graft failure following kidney transplantation. Current diagnostic strategies largely rely on biopsy findings and circulating donor-specific antibodies, but these approaches do not directly assess the immune effector mechanisms responsible for tissue injury.
NK cells have increasingly been recognised as key contributors to ABMR through antibody-dependent cell-mediated cytotoxicity. However, clinically practical methods for measuring this functional immune response have remained limited.
NK-CHAT Captured Functional Immune Activation
In the new proof-of-concept study, researchers evaluated NK-CHAT in 14 kidney transplant recipients within 6 months of transplantation. Seven participants had biopsy-confirmed ABMR, while seven showed no major abnormalities.
The assay measured NK cell activation after donor cells were exposed to recipient serum. Investigators specifically assessed CD107a degranulation and interferon-γ (IFN-γ) production longitudinally as markers of NK cell activity.
Researchers found that CD107a-based NK-CHAT activity was significantly higher in patients with ABMR compared with those without evidence of graft injury. Importantly, elevated activity was detectable early after transplantation, suggesting the assay may identify immune activation before substantial graft deterioration develops.
By contrast, IFN-γ production did not significantly differ between groups, indicating CD107a degranulation may represent the more sensitive functional marker for ABMR-associated immune responses.
Potential Role for Kidney Transplant Monitoring
The findings highlight the growing importance of functional immune biomarkers in kidney transplantation. Unlike conventional laboratory markers, NK-CHAT attempts to directly quantify the cytotoxic immune activity driving graft damage.
If validated in larger studies, the assay could potentially complement existing surveillance strategies, helping clinicians identify patients at increased risk of antibody-mediated rejection earlier in the post-transplant period.
Limitations and Future Directions
The authors acknowledged that the study was limited by its small sample size and short follow-up period. Larger multicentre investigations will be needed to determine the diagnostic accuracy, reproducibility, and clinical utility of NK-CHAT across broader transplant populations.
Nevertheless, the results provide early evidence that functional NK cell assays may offer a promising new approach for monitoring immune activation after kidney transplantation and improving long-term graft outcomes.
Reference
Kim JM et al. The natural killer–cellular humoral activation test as a functional biomarker of antibody-mediated rejection after kidney transplantation. Sci Rep. 2026. 10.1038/s41598-026-48024-1.
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